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B The chromodomain proteins that recognize the methylated lysines and recruit further interactors are the methyl readers. The dot plot visualized here depicts the cell types on the x -axis as labeled on the top.

The dot color represents the expression level, and the legend is provided above the plot. The cell types have been grouped based on their lineage in the polyps. Figure 5. A The writers include acetyltransferases with the catalytic HAT domain. B The bromodomain proteins that recognize the acetyl mark and recruit further interactors are the acetyl readers.

Figure 6. B The dot plot represents the expression profile of the different chromatin remodelers which interact with readers, writers, and erasers and bring about large-scale changes in the chromatin. The phylogenetic position of cnidarians together with the dynamic tissue turnover and regenerative capacity of Hydra make it a useful model system for tracing back the evolutionary trajectories of the underlying mechanisms of gene expression regulation.

Experiments on polyps have yielded insights into how the conserved cellular coordination is affected in a minimalistic body organization, remains conserved in vertebrates, and impacts the unique physiology of Hydra. Studies elucidating the epigenetic mechanisms operating at the transcriptional and post-transcriptional level in Hydra polyps are discussed in this review.

The size of H. No obvious sex chromosomes have been identified in Hydra till date. Additionally, transcriptome analysis resulted in the identification of approximately 81 probable long non-coding RNAs lncRNAs Wenger and Galliot, The Hydra genome is compacted and the gene expression is regulated by nucleosomes as observed in other animal species. There are only a few studies on histone variants in Hydra so far.

The chromatin of interstitial cells in Hydra cauliculata was found to be enriched with canonical histones during somatic and male germline differentiation, concomitant with condensation. Spermatocyte formation is accompanied by a transition from lysine-rich to arginine-rich chromatin, similar to the replacement of nucleosomes by protamines in higher metazoans during spermatogenesis.

In Hydra hymnae , which has arginine-rich histones, this transition does not occur. Moreover, protamine transitions were not detected in either species Moore, ; West, Indeed, Hydra spp. The genomic organization of the histone repertoire encoded by H. Among the variants identified for H2A were two H2A. X-type histones, which are known to play a role in the early DNA damage response.

This result, together with their higher expression in the gastric column, suggests a role for H2A. X in protecting the constantly dividing genomes of Hydra stem cells. Other histone variants identified include H2A. Z, macroH2A, H3. Phylogenetic analysis revealed high amino acid variation across cnidarian H2A and H2B histones, particularly between H. Notably, a replication-dependent H3. The replication dependency and functions of histone variants other than H2A.

X are yet to be characterized in Hydra , but their presence in polyps suggests that they may play broadly conserved roles in genome regulation. Among the various histone modifications and modifiers, studies in Hydra have dealt with histone methylation and acetylation. Typically, these are well-established marks on histones that are associated with transcriptional regulation.

In this review, we have focused on these marks and their modifiers including writers and erasers. Early studies used in situ hybridization for localizations of epigenetic modifiers and immunofluorescence to identify their target modifications. The modification in addition to the histone variants may serve to silence sperm chromatin in the absence of protamines, thereby playing a conserved role in a divergent trait.

Further, EED overexpression was countered by proteasomal degradation to retain the wild type EED expression pattern, suggestive of position-dependent proteostasis in the body column of Hydra Khalturin et al. An investigation into the localization of Hydra PRC2 complex proteins EED and EZH2 revealed the encoding mRNAs to be highly expressed in the interstitial cells, whereas the corresponding proteins were enriched in the ectodermal epithelial cells.

H3K27me3 per se was enriched in interstitial cells. Interestingly, the YY1 protein was detected in nuclei of ectodermal epithelial cells, though their membranes also stained positive. It is therefore plausible that PRC2 recruitment plays a role toward the maintenance of this cell lineage as well Matt, A conserved localization at open chromatin regions was observed for H3K4me2 and H3K4me3 in whole and head-regenerating polyps and higher levels of H3K4me2 were correlated with the enhancer regions of the Hydra genome.

However, the typical higher enrichment ratios did not predict the promoter and a potential enhancer of the wnt3a locus Murad et al. Enhancer RNA transcription is also indicative of active enhancers and active promoter-enhancer interactions Kim et al. It is plausible that the cnidarian stem cells possess the bivalent chromatin modification signature that keeps lineage-specific genes in a transcriptionally poised state, the confirmation of which would require the detection of H3K4me3 and H3K27me3 co-enrichment using techniques such as sequential ChIP.

It may also be of interest to determine how the H3K27me3-negative interstitial cell population differs from those positive for the modification. The expression pattern of the various components of the modification machinery involved in writing, reading, and erasing the methylation of histones in different cell types of Hydra is shown in Figure 4.

In addition to the male germline cells which were previously shown to have EZH2 expression, scRNAseq data analysis also led to the identification of female germline stem cells and the different types of interstitial stem cells or progenitor cells to have expression of this gene.

EED which was upregulated during embryogenesis was detected in the female and male germline stem cells and to a lesser extent in few interstitial progenitor cell types. Histone H3 lysine 27 acetylation H3K27ac was found to be a more reliable signature of enhancers in Hydra and was also enriched at the open promoter-proximal regions, consistent with its role in transcriptional activation.

To understand the dynamics of H2K27ac occupancy during regeneration, ChIP-sequencing was performed on chromatin isolated from regenerating tips of Hydra at various time points. H3K27ac was most enriched at the putative wnt3a enhancer in the head region and the promoter-proximal region 4 h post-decapitation Murad et al. H3K27ac increases at the putative enhancers of head-related genes upon disruption of axis patterning, suggesting that H3K27ac activates axis patterning enhancers that are repressed by H3K27me3 in other tissues Reddy et al.

A similar occupancy-to-expression trend is observed for H3K27ac in N. Histone hyperacetylation by HDAC inhibition results in diminished head and foot boundaries, attributed to the de-repression of the cell cycle genes in these differentiated regions. Bud detachment failure is also observed, consistent with a foot boundary defect, which eventually promotes ectopic body axes.

HDAC activity in vivo is predicted to be dependent on phosphatidylinositol, based on the marked enrichment of its biosynthetic pathway components in the head and foot and HDAC enrichment in the body column. Here, it has been demonstrated that Hdac2 interacts with SoxB2 and regulates the differentiation of neurons from stem cells Flici et al. Later it has been reported that the inhibition of Hdac2 affects the migration of proliferative cells and the formation of a blastema, thus affecting regeneration Flici and Frank, Other acetyltransferases appear to be expressed in stem cells and differentiated cell types of all lineages and could be playing a role in taxon-specific functions in Hydra.

There have been no studies that investigate the expression patterns of the reader and eraser proteins of histone acetylation and few predictions can be drawn from the scRNA-seq data for future studies. The BRD2 protein shows an expression in multiple cell types with higher levels in progenitor cell types which could be a predictor of its function. It will be useful to understand how active enhancers in the head retain acetylation in the background of HDAC activation.

DNA methylation in Hydra is yet to be functionally characterized, with only its genomic and transcriptomic presence quantitatively determined so far. Both approaches respectively yielded m 5 dC frequencies of 2. Since the genome of Hydra has a low GC content, the level of non-CpG methylation might be significant and the location of the modifications in the gene bodies may play a role in transcriptional regulation as seen in some other animal species.

In addition, the level of m 6 dA positively correlates with transcription Pacini et al. The sequence context and function of DNA methylation in Hydra are yet to be determined. Single-cell transcriptomics data Siebert et al. Orthologs of m 5 dC writers and erasers are highly upregulated in the female germline, suggesting that m 5 dC may be dynamically regulated for oocyte reprogramming, while a high level of its reader MBD2 could function to silence oocyte chromatin Figure 6A.

In contrast, moderate DNMT3a levels observed in differentiating cells coupled with low TET2 levels may correspond to an increase in cytosine methylation during differentiation. DNMT1 appears to be high in stem cells as evident from the scRNA-seq analysis, concomitant with its role in methylation maintenance in mitotic cells Bestor and Ingram, Putative transcripts of proteins involved in m 6 dA metabolism are similarly enriched in the female germline and low in terminally differentiated cells Figure 6A.

Mitotic accumulation of m 6 dA by DNA polymerase could potentially counteract the overall low methyltransferase levels toward the maintenance of the mark Musheev et al. Contemporary studies using other cnidarians may provide some clues and motivation toward understanding the biological role of DNA methylation. There is a large level of variation in the level of methylation across non-bilaterian genomes de Mendoza et al. A comprehensive study on a large cohort of eumetazoans reported an m 5 dC frequency of 1.

Reanalysis of the Nematostella cytosine methylome revealed a characteristic bimodal distribution of genes with low and high C p G abundances, though no significant correlation with expression level was observed Nanty et al.

C p G methylation occurs mutually exclusive of H3K4me3 in Nematostella , and hence the latter may inhibit the methylation of the underlying DNA as it does in bilaterians Schwaiger et al. Studies on corals suggest gene body C p G methylation promotes gene expression rigidity Dixon et al. Interestingly, Myxosporea, another class of cnidarians, lacks both the DNMTs and cytosine methylation as identified by a study on the genomes, transcriptomes, and proteomes of the various cnidarian species Kyger et al.

This may be functionally correlated with the presence of its intermediate product—hm 5 dC—in the P. A recent comparative study of genome-wide DNA methylation at the root of the animal phyla has thrown light on the conserved mechanisms of DNA methylation at the root of animal evolution. This study has clearly demonstrated the occurrence of hypermethylated genomes, especially in Amphimedon a marine sponge similar to vertebrates indicating convergent evolution de Mendoza et al.

However, further detailed studies are required to elucidate the DNA methyl code both at CpG and non-CpG locations in the context of gene regulation and other functions. The development of next-generation sequencing technologies facilitated transcriptomic profiling of tissue samples. Four miRNAs were found in the freshwater cnidarian, all novel, including the cnidarian-specific miR in common with N.

The H. However, barely half the sRNA reads mapped to the draft H. Another study reported a similar genome-transcriptome disparity in H. Comparative analysis of sRNAs expressed in both whole and regenerating H. Additionally, analyses of H. Analysis of the miRNA dataset generated by Krishna et al. This was also found to be the case for N. Additionally, homologs of key miRNA pathway components have been identified in the transcriptomes of Hydra and the anthozoans Nematostella and Acropora.

The miRNA components in Cnidarians exhibit very specific expression patterns and putative roles during the development of the organism. The mechanism of action of these molecules appears to be more similar to that in plants than in bilaterian animals based on their target complementarity, mode of gene regulation, and post-transcriptional modifications Moran et al.

Notably, cnidarians express HYL1, which is a partner of Dicer typically employed by plants Grimson et al. Another striking similarity between plant and cnidarian miRNAs is their near-perfect complementarity to target transcripts, which promotes transcript cleavage instead of ribosome stalling. Concomitantly, cleavage products for 2 out of 5 putative H. Nematogalectin-related 2 mRNA was determined to be a target of cnidarian miR , and both were observed to co-localize in the nematocytes of N.

Interestingly, the localization of miR in primary polyps of N. The closest homolog of the uncharacterized N. It is thus possible that miR regulates a different protein in Hydra , which could explain the divergence in its localization between the two cnidarians if found to be the case. Taken together, these studies are suggestive of a common ancestral miRNA mechanism that diverged in higher metazoans, presumably enabling more rapid and dynamic post-transcriptional responses to stimuli Gu et al.

Figure 7. Divergent localization of miR between the two cnidarians is observed, with the miRNA expressed at the oral end of Nematostella but excluded from the oral and aboral ends of Hydra. This presumably explains the divergent localization. Knockdown of genes in Hydra by RNAi is a common experimental practice, suggesting that the cnidarian harbors the functional machinery to effect the same. However, functional studies on this gene regulation system as well as miRNA functions are currently lacking.

A study in N. The Ago2 component of the RNAi machinery shows a significantly higher expression in the endodermal lineage relative to the ectodermal lineage Figure 6C. Similar perturbation studies in Hydra could be useful for understanding the role of miRNAs in its unique biology. Sequencing of the H. The sRNA-seq analysis by Krishna et al. Notably, potential piRNAs that mapped onto histone genes reduced in abundance during head regeneration while the histone-encoding transcripts were themselves upregulated at the corresponding time points, suggesting that these sRNAs may regulate histone abundances.

Multiple other piRNA-like RNAs are also differentially regulated during head regeneration with putative roles in regulating the expression of target genes in the regenerating tissue Krishna et al. Given that the piRNA-PIWI protein complexes contribute to transcription gene silencing, it is plausible that piRNA-mediated gene regulation may affect the transcription of histones and other genes.

The observed target gene upregulation corresponding to piRNA-like RNA downregulation implies that such transcriptional silencing is reversible, at least in regenerating Hydra tissue. Additionally, differentiated Hydra cells may employ other gene regulatory mechanisms including histone methylation to repress genes.

The putative piRNA pathway in Hydra has been characterized by independent studies. In mature male germline cells, however, only a single punctum was visible-resembling chromatoid bodies observed and characterized in higher metazoans as sites of stable transposon repression by DNA methylation. Additionally, both these homologs possess critical symmetrical dimethylarginine residues at their N-termini Lim et al. Somatic functions have also been demonstrated for Hywi, with lineage-specific non-transposon RNA targets also identified.

Hywi RNAi lines disintegrate within 12 days of hatching due to epithelium disruption and are impaired in transposon silencing, confirming the functionality of piRNAs in transposon repression in somatic cells Juliano et al. The scRNA-seq data also corroborates the presence of the various piRNA interacting machinery in both germline stem cells, somatic stem cells, and few somatic differentiated cells as well Figure 6C.

The pathway may promote interstitial cell differentiation in H. Taken together, these studies outline roles for the cytoplasmic piRNA pathway in both germline and somatic cnidarian stem cell lineages, which may respectively restrict mutagenesis during gametogenesis and clonal propagation and, to some extent, regulate gene expression.

The somatic function of PIWI is therefore ancient and may have been lost in few higher metazoans, while nuclear functions of the germline piRNA pathway appear to have evolved later. Multicellular organisms are an ensemble of different cell types with distinct functions orchestrated spatially to achieve a phenotype.

The development of these organisms from a single cell requires precise regulation of cell fates in a spatiotemporal manner. Cis -regulatory elements CREs facilitate coordinated regulation of various sets of genes required for development and physiology Levine, These elements are short DNA sequences mostly, non-coding that are bound by TFs or other regulatory molecules and influence gene regulation Ong and Corces, Typically, CREs can be categorized into promoters and enhancers.

Promoters are regions with overlapping TSSs and contain single to multiple CREs that allow binding of the transcription initiation complex to attain gene transcription Lenhard et al. Enhancers are located at varying distances from their target genes and amplify the transcription by regulating the promoter Shlyueva et al. Enhancers play a crucial role in context-specific gene regulation and mutations in these regions lead to altered morphology or physiology.

Due to this reason changes in enhancer sequences often result in the evolution of novel functions Carroll, ; Frankel et al. Therefore, it is important to understand the evolution of such CREs associated with eumetazoan-specific functions. However, there is very little information available regarding their nature and regulation at the base of Eumetazoa where major transitions such as cell type and phenotype evolution occurred.

A first step toward understanding the evolution of enhancers is the identification of CREs in genomes of early diverging eumetazoan phyla such as Cnidaria. Their functional relevance can be elucidated by studying their dynamics under different experimental conditions. Toward this, a study was performed in N. This study indicated that bilaterian enhancer characters are conserved in N.

In Hydra , Wnt signaling has been shown to play a vital role in the organizer formation and is associated with massive transcriptional changes Reddy et al. This phenomenon is crucial in the evolution of body axis patterning. In a recent study by Reddy et al. The list of these genes includes many of the important transcription factors such as CnGsc , HyBra , CnAsh , CnOtx that play a seminal role in the head organizer formation. This study provided significant insights into the enhancer-mediated regulation of organizer genes Reddy et al.

Hydra is known for its extraordinary regeneration capacity and organizer formation is a critical step in the head regeneration process. A recent study used assay for transposase-accessible chromatin ATAC -seq and histone marks to identify the enhancers involved in the regeneration process. Murad et al. Notably, enrichment of CnGsc binding motifs was observed on the enhancer elements found during the regeneration time course which is important in head patterning in Hydra.

Based on the initial studies, H3K27ac has proven to be a reliable histone modification mark to identify the enhancer elements with more confidence. However, in Hydra , H3K4me3 also exhibits colocalization at the enhancer elements which needs to be further studied. Additional efforts are required toward the identification of the enhancer elements involved in precise functions such as cell type determination and their functional validation. The conservation of the occupancy of histone marks is depicted in Figure 8A.

Figure 8. Regulation of gene expression by cis -regulatory elements in Cnidaria and Vertebrata. A Comparison of the occupancy of various histone modifications on putative enhancer regions in Cnidarians and vertebrates. The classical marks associated with enhancer regions in vertebrates have been identified to localize to putative enhancer regions in both N. Model based on data from Schwaiger et al.

Studies in the s and s first reported the morphology of cells in various Hydra spp. Lentz, ; Weissman et al. Interstitial cells in Hydra littoralis were observed to have electron-dense chromatin at the nuclear periphery consistent with heterochromatin, and exhibited chromatin aggregation and increased nucleolar size during somatic differentiation Lentz, In spermatids of H. Surprisingly, while embryonic depletion of the Lamin protein was found to be lethal in H. This robustness to lamina perturbation is attributed to fewer lamina-binding proteins compared to higher metazoans Klimovich et al.

Vertebrate embryonic stem cells are also indifferent to Lamin depletion, highlighting their dispensability in stem cells across metazoans Stewart and Burke, ; Kim et al. Chromosome territories and evolutionarily conserved patterns and sizes of DNA replication foci have also been identified in H. Assay for transposase-accessible chromatin-seq mapping of the H. Among these, the promoter-proximal regions exhibited the highest accessibility, followed by the intergenic ones.

The accessibility of the wnt3a locus that encodes the head organizer morphogen Wnt3a in the regenerating tissue, was found to peak 4 h post-decapitation at its promoter and downstream enhancer regions. A similar accessibility pattern for wnt3a was observed in the hypostome, in agreement with its role in head organizer maintenance Murad et al. Open chromatin profiles have been detected at the promoters of highly expressed genes in H.

It is plausible that this upstream region is a silencer of wnt3a and may be bound by head repressors such as Sp5 in non-hypostome cells Vogg et al. This hypothesis may be tested by performing ChIP of Sp5 followed by quantitative PCR for the upstream region in whole polyps versus hypostome tissue, while a functional validation mandates deletion of the putative silencer. ATAC-seq mapping in neurons of the cnidarian N.

A positive correlation between gene accessibility and transcription has been observed for most circadian rhythm-regulated gene promoters in the starlet sea anemone N. In a recent study, Reddy et al. Unlike earlier divergent phyla, all negative elongation factor complex NELF homologs were identified in H. The presence of chromatin loops and higher-order assemblies such as the topologically associating domains TADs is yet to be determined in polyps.

TADs may therefore be an architectural feature unique to bilaterian genomes although this phenomenon may be independent of known homologs of CTCF. HyYY1 was observed to be enriched in the nuclei of ectodermal epithelial cells in the gastric column, head and foot regions, suggestive of a region-independent role. However, it was also detected on the membranes of these cells, though this is likely an artifact of antibody binding to non-YY1 membrane proteins.

However, the histone marks installed by PRC2 H3K27me3 are detected only in the interstitial cells, and therefore the detection of Polycomb proteins in ectodermal epithelial cells is counterintuitive Matt, KLF7 is enriched in epithelial stem cells, KLF8 is specific to ectodermal epithelial stem cells and KLF3 is found in both interstitial and ectodermal epithelial stem cells Hemmrich et al.

Phylogenetic analysis revealed that these Hydra KLF orthologs cluster with their respective non-vertebrate orthologs Figure 9. In contrast, YY1-like clusters with other YY1 orthologs, supporting its role as a putative chromatin organizer. Figure 9. Branch lengths are proportional to the tree scale bar. Scale bar represents the number of substitutions per site. Names of all Hydra proteins are indicated in red. Most of the studies on epigenetic modifiers focus on monitoring the transcript levels of the proteins with an evident disparity in mRNA-protein localizations for a few of them.

Studies that investigate protein localization and interactions directly will provide better insight into the role of the resultant modification and regulatory nucleic acids. Additionally, single-cell ATAC-seq could provide the chromatin accessibility profiles of individual cells Buenrostro et al. Wherever information in addition to the scRNAseq is available for many proteins and modifications, we have speculated their role in the unique physiology of Hydra and its regenerative capacity.

Further validations involving protein levels, the activity of the proteins, the dynamics of target modifications, and the post-transcriptional mechanisms are necessary to understand the complex epigenetic regulation of the developmental processes and regeneration in Hydra. The landmark studies in Hydra alluding to the above are listed in Table 1.

A graphical summary of the validated and predicted functions of epigenetic regulators in Hydra is provided in Figure Table 1. Tabular summary of the epigenetic regulation studies in Hydra are reviewed here. Figure A graphical summary of the verified and scRNA-seq predicted roles of epigenetic regulators and histone modifications in Hydra.

The head, gastric column, and foot regions are respectively demarcated by the expression of the master regulators Wnt3a and other proteins , FoxO, and NK2. Epigenetic regulators enriched in the gastric column promote stem cell maintenance, while those at the apicobasal termini promote differentiation. Enhancers controlling head organizer genes are active in the head and repressed elsewhere by H3K27me3. Demethylation and acetylation of H3K27 switches on head-specific enhancers and the activated HDACs could be acting on the genes that play a role in proliferation and body-column maintenance.

Head organizer genes become active at the hypostome, which may reflect head enhancer activation in ectodermal cells inset. H3K27 modification-dependent enhancer regulation is also relevant in the context of Hydra regeneration, wherein the activation of head organizer genes post decapitation facilitates head formation at the regenerating tip. Apart from the studies suggested in each section of this review, the following investigations may further our understanding of the epigenetic regulation and its transgenerational inheritance in Hydra :.

Mapping the epigenomes of Hydra sperm and oocyte to identify the conserved determinants of transgenerational inheritance. Here, external fertilization is advantageous toward the collection of gametes. Delineating the epigenetic regulation of cell fate determination and axis patterning in homeostatic and regenerating polyps could provide evolutionary insights into the process.

Performing high-resolution proteomic analyses at a single cell level Ma et al. The dynamics and effects of DNA methylation have not been investigated in detail in Hydra. The continuous proliferation and differentiation of cells in Hydra offers an excellent paradigm to gain insights into the ancestral roles of the DNA modifying machinery during metazoan evolution. DNA methylation changes are associated with aging and age-related diseases. Hydra is an immortal organism and it does not exhibit typical aging-related disease phenotypes.

Thus, understanding the maintenance of DNA methylation in Hydra will provide insights into the aging process. Recent studies have elucidated the conservation of cis -regulatory DNA elements in the regulation of developmental genes across multiple canonical model organisms Plessy et al.

Investigating the conserved nature of Hydra enhancer elements in higher organisms will allow us to understand the fundamental roles of these regulatory regions and how they were adapted into distinct signaling pathways as the processes diverged. The redundancy of enhancer-mediated regulation can also be addressed well in organisms such as Hydra. They exhibit the processes of embryonic development, budding, and regeneration which offer an opportunity to look at the regulation of the same genes in diverse physiological contexts.

Especially, close phylogenetic relationship with Bilateria and occurrence of conserved molecular machinery, cell types, and developmental processes provides a unique opportunity to identify the conserved cis -regulatory elements responsible for the evolution of eumetazoan cell types and functions. The organization of chromatin into active and inactive compartments aids in the efficient regulation of gene expression in a spatiotemporally appropriate manner.

However, other mechanisms based on the PcG components, transcription-based organization, and arrangement of the genomic regions in an alternating active-inactive format contribute toward achieving this Matthews and White, Along with the chromatin level regulation of gene expression, there is an additional level of post-transcriptional checkpoints in the cells.

A part of this process has been discussed in the review and the other part involves chemical modification of the RNA species inside the cells. Various types of RNA modifications are reported, and the occurrence of the ADAR machinery has been identified in organisms at the root of animal phyla such as Ctenophores, Placozoans, sponges, and Cnidarians Keegan et al. Among the RNA modifications, an important modification is the m 6 A on different RNA species in the cell which targets it for degradation or stabilizes it for translation Zaccara et al.

The various components of the modification machinery including the writers, erasers, and readers of this modification in Hydra have not yet been identified and the role of these molecules and the modified RNA in the physiology of Hydra will be interesting to study in the context of cellular differentiation during regeneration and budding. AP and AG contributed to design concept, collected and analyzed literature, wrote bulk of the manuscript, and prepared table and figures.

PCR and SG provided critical inputs as the corresponding authors, wrote sections of the manuscript, and obtained funds. All authors approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Alexandrova, O. Oogenesis in Hydra: nurse cells transfer cytoplasm directly to the growing oocyte. Chromosoma , — Allan, J. Regulation of the higher-order structure of chromatin by histones H1 and H5. Cell Biol. Aravin, A.

Genes Dev. Cell 31, — Bannister, A. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature , — Bartke, T. Nucleosome-interacting proteins regulated by DNA and histone methylation.

Cell , — Barton, S. Role of paternal and maternal genomes in mouse development. Baumgarten, S. Evidence for mi RNA-mediated modulation of the host transcriptome in cnidarian—dinoflagellate symbiosis. Becker, C. Spontaneous epigenetic variation in the Arabidopsis thaliana methylome.

Bernstein, B. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Bestor, T. Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Blewitt, M. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet. Bode, H. Quantitative analysis of cell types during growth and morphogenesis in Hydra.

Wilhelm Roux Arch. Boehm, A. FoxO is a critical regulator of stem cell maintenance in immortal Hydra. Bosch, T. Stem cells of Hydra magnipapillata can differentiate into somatic cells and germ line cells. Bradshaw, B. Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata. Elife 4:e Google Scholar. Browne, E. The production of new hydranths in hydra by the insertion of small grafts.

Buenrostro, J. Single-cell chromatin accessibility reveals principles of regulatory variation. Burnett, A. The nervous system of Hydra. Types, distribution and origin of nerve elements. Campbell, R. Tissue dynamics of steady state growth in Hydra littoralis. Patterns of tissue movement. Carone, B. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.

Carroll, S. Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell , 25— Carvan, M. III, Kalluvila, T. Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish. PLoS One e Chamorro-Garcia, R. Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice.

Health Perspect. Chapman, J. The dynamic genome of Hydra. Cingolani, P. BMC Genomics Cummings, S. Head regeneration and polarity reversal inHydra attenuata can occur in the absence of DNA synthesis. Wilhelm Roux. Dabe, E. DNA methylation in basal metazoans: insights from ctenophores.

Dalal, Y. Structure, dynamics, and evolution of centromeric nucleosomes. David, C. A quantitative method for maceration of hydra tissue. Davis, R. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, — Convergent evolution of a vertebrate-like methylome in a marine sponge. The emergence of the brain non-CpG methylation system in vertebrates. Dhalluin, C. Structure and ligand of a histone acetyltransferase bromodomain. Di Giammartino, D.

KLF4 is involved in the organization and regulation of pluripotency-associated three-dimensional enhancer networks. Dixon, G. Role of gene body methylation in acclimatization and adaptation in a basal metazoan. Bimodal signatures of germline methylation are linked with gene expression plasticity in the coral Acropora millepora.

Evolutionary consequences of DNA methylation in a basal metazoan. Dixon, J. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Dou, Y. Duncan, E. Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation.

Duttke, S. Identification and dynamic quantification of regulatory elements using total RNA. Genome Res. Eickbush, T. The histone core complex: an octamer assembled by two sets of protein-protein interactions. Biochemistry 17, — Eirin-Lopez, J. Origin and evolution of chromosomal sperm proteins.

Bioessays 31, — Fan, Y. Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Farrelly, L. Feng, S. Conservation and divergence of methylation patterning in plants and animals. Flici, H. An evolutionarily conserved SoxB-Hdac2 crosstalk regulates neurogenesis in a cnidarian.

Cell Rep. Frankel, N. Morphological evolution caused by many subtle-effect substitutions in regulatory DNA. Fu, Y. N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas. Fuks, F. Nucleic Acids Res. Gahan, J. Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarian Nematostella vectensis. Gajigan, A. A microRNA regulates the response of corals to thermal stress. Galande, S. The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1.

Gebert, L. Regulation of microRNA function in animals. Genikhovich, G. Discovery of genes expressed in Hydra embryogenesis. Gierer, A. Regeneration of hydra from reaggregated cells. New Biol. Greenberg, M. The diverse roles of DNA methylation in mammalian development and disease. Greer, E. Grens, A. CnNK-2, an NK-2 homeobox gene, has a role in patterning the basal end of the axis in hydra. Grimson, A. Gu, K. Regulating gene expression in animals through RNA endonucleolytic cleavage.

Heliyon 4:e Hajkova, P. Epigenetic reprogramming in the germline: towards the ground state of the epigenome. R Soc. B Biol. Hammoud, S. Distinctive chromatin in human sperm packages genes for embryo development. Hao, Z. N6-Deoxyadenosine methylation in mammalian mitochondrial DNA.

Cell 78, — Harris, C. A DNA methylation reader complex that enhances gene transcription. Science , — Hassel, M. Electrophoresis 31, — Heger, P. The chromatin insulator CTCF and the emergence of metazoan diversity. Heintzman, N. Finding distal regulatory elements in the human genome.

Hemmrich, G. Molecular signatures of the three stem cell lineages in hydra and the emergence of stem cell function at the base of multicellularity. Henikoff, S. We need to list all the active sessions. We use the sessions command from the ts module. Here we can see that there exists a Session 3 for aarti user that is active.

Back to the session output, we saw that the aarti user has session 3. We need to connect to that particular session using the remote command of the ts module. As we can see in the image that we were able to get the remote desktop session for the aarti user from the raj user access.

This is the process that a Session Hijacking is possible for the Remote Desktop services. To discuss mitigation, we first need to detect the possibility of the attack. As all the services on Windows, Remote Desktop also creates various logs that contains information about the users that are logged on, or the time when they logged on and off with the device name and in some case IP Address of the user connecting as well. There exist various types of logs regarding the Remote desktop service.

While connecting to the client the authentication can either be successful or failure. With both these cases, we have different EventIDs to recognise. The authentication logs are located inside the Security Section. EventID Authentication process was successful. EventID Authentication process was failure. Then we have the Logon and Logoff events. Logon will occur after successful authentication.

Logoff will track when the user was disconnected from the system. These particular logs will be located at the following:. At last, we have the Session Connection Logs. This category has the most Events because there are various reasons for disconnection and it should be clear to the user based on the particular EventID. These logs are located at the following:. We can see that in the given image the aarti user was reconnected.

This is a log entry from the time we performed the Session Hijacking demonstration. That means if an attacker attempts that kind of activity, you might be looking for this kind of logs. For Mitigation, we can set a particular time limit for disconnected sessions, idle Remote Desktop services that might be clogging up the memory usage and others.

These policies can be found at:. When implemented, these policies will restrict the one necessity required by the session hijacking i. Hence, mitigation the possibility of Session Hijacking altogether. One of the things to notice before getting on with the attack is that DoS Attacks through Remote Desktops are generally not possible. In this demonstration, we will be using a Windows 7 machine.

Before getting to the exploit, Metasploit has an auxiliary that can be used to scan the machine for this particular vulnerability. As it can be observed from the image below that the machine that we were targeting is vulnerable to a DoS attack. Now that we have the confirmation for the vulnerability, we can use it to attack our target machine. This attack is named as max channel attack.

This attack works in the following method. Firstly, it detects the target machine using the IP Address. Then it tries to connect to the machine through the RDP service. When the target machine responds that it is ready to connect, the exploit sends large size packets to the machine. The size of the packets is incremental until it becomes unresponsive. In our demonstration, we can see that it starts with a bytes packet. It will continue to send packets until the target machine is unable to handle those packets.

BlueKeep was a security vulnerability that was discovered in Remote Desktop Protocol implementation that can allow the attacker to perform remote code execution. It was reported in mid Windows Server and Windows 7 were the main targets of these vulnerabilities. But since this attack is based on heap corruption, there is a chance that if the configuration of the exploit is incorrect it could lead to memory crashes.

Metasploit contains an auxiliary scanner and exploit for BlueKeep. It requires the IP Address of the target machine. We are running this against a Windows 7 machine with Remote Desktop enabled. We see that it returns that the target is vulnerable. Since we now know that the target is vulnerable, we can move on to exploiting the target.

After selecting the exploit, we provide the remote IP address of the machine with the particular target. It can vary based on the Operating System; for Windows 7 use the target as 5. We can see that it connects to the target and first checks if it is vulnerable. Then it proceeds to inflict the heap corruption that we discussed earlier and results in a meterpreter shell on the target machine. There are a lot of mitigations that can help a wide range of environments.

It can include installing the latest updates and security patches from Microsoft or as the NSA suggests to disable the Remote Desktop Service until use and disable after use. The BlueKeep attacks can be mitigated to the most extent by upgrading the Operating System from Windows 7. There is a long list of other mitigation steps that can be implemented such as implementing an Intrusion Detection Mechanism and other defense mechanisms.

One of the steps that can be taken with immediate effect is changing the port number on which the Remote Desktop operates on. This although seems that is not a big defense mechanism but if done correctly, the attacker might not even look for this angle. To do this, we need to make changes to the registry. Open the registry editor and proceed to the following path:. Here we have the Port Number as shown in the image.

Change it to another value and save your changes and now the RDP will be running on the specified port. In our demonstration, we changed the port to from We can use the rdesktop command from Linux to connect to the Windows Machine as shown in the image given below. As we are familiar with the typical Man-in-the-Middle Attacks that the attacker most likely impersonates the correct authentication mode and the user who is unaware of the switch unknowingly provides the correct credentials.

Some other methods and tools can be used to perform this kind of attack but the SETH toolkit is the one that seems elegant. We start with cloning it directly from its GitHub Repository and then installing some pre-requirements.

In this case, it is eth0. Here we see that the attack has been mounted and is ready for the victim. It asks for the credentials to connect as any original security authentication prompt. Next, we have is the Certificate Manager. Here we can see that there seems to be a conflict regarding the Server Name and Trusted Certifying authority. This is usually quite similar to the window that asks for saving the certificate. As soon as the connection is established, we can go back to the Kali Linux where we mounted the attack.

We can see that it was able to capture the NTLM hash as well as the password that was entered by the victim. This completes the Man-In-the-Middle Attack. Remote Desktop Service is one of the most used services. It was quite important when it was brought by Microsoft but the Pandemic and Work from Home culture has made it the necessity of every enterprise.

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