Genome-wide maps of H3K9me3 with tethered heterochromatin machinery
Ontology highlight
ABSTRACT:
ORGANISM(S): Neurospora crassa
PROVIDER: GSE103926 | GEO | 2017/09/16
SECONDARY ACCESSION(S): PRJNA407574
REPOSITORIES: GEO
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Project description:Neurospora importin alpha compromises H3K9me3 and cytosine methylation levels through inappropriate localization of the heterochromatin machinery
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Project description:Gene silencing by heterochromatin plays crucial roles in cell identity and development. However, the function of heterochromatin components is not fully understood. Here, we characterize the localization, the biogenesis and the function of an atypical heterochromatin, which is simultaneously enriched in the typical heterochromatin mark H3K9me3 as well as in H3K36me3, histone mark usually associated with gene expression. This dual heterochromatin forms on 3,015 regions in the genome of mouse embryonic stem cells and relies on the histone methyltransferases SET Domain Bifurcated 1 (SETDB1) and Nuclear Set Domain containing proteins (NSD) to generate H3K9me3 and H3K36me3, respectively. Upon SETDB1 removal, dual domains loose both trimethyl marks, gain epigenomic signatures of active enhancers, and come into long range contact with upregulated genes, suggesting that it is a major pathway by which gene expression is controlled by heterochromatin. In differentiated tissues, a large subset of these dual domains is destabilized and become enriched in active enhancer marks, providing a mechanistic insight into the involvement of heterochromatin in development and the maintenance of cell identity.
2022-01-25 | GSE171749 | GEO
Project description:Both RNAi-dependent and -independent mechanisms have been implicated in the establishment of heterochromatin domains, which may be stabilized by feedback loops involving chromatin proteins and modifications of histones and DNA. Neurospora crassa sports features of heterochromatin found in higher eukaryotes, namely cytosine methylation (5mC), methylation of histone H3 lysine9 (H3K9me) and HETEROCHROMATIN PROTEIN-1 (HP1), and provides a model to investigate heterochromatin establishment and maintenance. We mapped the distribution of HP1, 5mC, H3K9me3 and H3K4me2 at 100bp-resolution and explored their interplay. HP1, H3K9me3 and DNA methylation were extensively colocalized and defined 44 heterochromatic domains on linkage group VII, all relics of repeat-induced point mutation (RIP). Interestingly, the centromere was found in a striking ~350kb heterochromatic domain with no detectable H3K4me2. 5mC was not found in genes, in contrast to the situation in plants and animals. H3K9me3 is required for HP1 localization and DNA methylation. Here, we show that localization of H3K9me3 is independent of 5mC or HP1 at virtually all heterochromatin regions. In addition, we observed complete restoration of DNA methylation patterns after depletion and reintroduction of the H3K9 methylation machinery, indicating that the signals for de novo heterochromatin formation lie upstream of H3K9 methylation. These data show that A:T rich RIPâd DNA efficently directs methylation of H3K9, which in turn, directs methylation of associated cytosines. Immunoprecipitation experiments using antibodies to 5mC, H3K9me3, epitope-tagged HP1, and H3K4me2 were performed. The immunoprecipitate fraction was labeled with Cy5 and the total input was labeled with Cy3. Samples were hybridized to a N. crassa LGVII tiling path microarray.
2010-05-15 | E-GEOD-12690 | biostudies-arrayexpress
Project description:Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment, we generated an inducible system to convert embryonic stem cells (ESCs) to 2C-like cells. This conversion is marked by a global reorganization and dispersion of H3K9me3-heterochromatin foci, which are then reversibly formed upon re-entry into pluripotency. Profiling the chromatin-bound proteome (chromatome) by genome capture of ESCs transitioning to 2C-like cells, we uncover chromatin regulators involved in de novo heterochromatin formation. We identified TOPBP1 and investigated its binding partner SMARCAD1. SMARCAD1 and TOPBP1 associate with H3K9me3-heterochromatin in ESCs. Interestingly, the nuclear localization of SMARCAD1 is lost in 2C-like cells. SMARCAD1 or TOPBP1 depletion in mouse embryos lead to developmental arrest, reduction of H3K9me3 and remodeling of heterochromatin foci. Collectively, our findings contribute to comprehending the maintenance of chromocenters during early development.
2023-04-18 | PXD019703 | Pride
Project description:Regulation of heterochromatin is critical for genome stability. Different states of methylated H3K9 have been discovered with distinct roles in heterochromatin formation and silencing. However, the control of the transition from H3K9me2 to H3K9me3 is still unclear. Here we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining the global nucleosome organization in fission yeast. We identified several key factors involved in heterochromatin silencing to interact genetically with Abo1: the histone deacetylase Clr3, the H3K9 methyltransferase Clr4, and the HP1 homologue Swi6. Cells lacking Abo1 display an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin had increased H3K9me2 but decreased H3K9me3 levels compared to wild type. In contrast, facultative heterochromatin regions, show both reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both centromeres and subtelomeres, but not in a subset of heterochromatin islands. Our work uncovers a new role for Abo1 in supporting Clr4 activity and allowing for the transition of H3K9me2 to H3K9me3 in telomeric and centromeric heterochromatin.
2020-04-13 | GSE125911 | GEO
Project description:Domains of transcriptionally repressed heterochromatin, decorated by histone 3 lysine 9 trimethylation (H3K9me3), are reduced in embryonic stem cells compared to fully differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein coding genes, in natural embryologic development, has not been described. We developed a novel, antibody-independent method to isolate and map compacted heterochromatin from low cell number samples. Unexpectedly, we uncovered extensive high levels of H3K9me3-decorated, compacted heterochromatin at protein coding genes in early, uncommitted cells in the three germ layers, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type-specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed that H3K9me3 heterochromatin is required to maintain cell lineage fidelity. We propose a key role for chromatin-based restriction of gene activity via H3K9me3 during embryologic development
2018-10-31 | GSE114197 | GEO
Project description:Domains of transcriptionally repressed heterochromatin, decorated by histone 3 lysine 9 trimethylation (H3K9me3), are reduced in embryonic stem cells compared to fully differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein coding genes, in natural embryologic development, has not been described. We developed a novel, antibody-independent method to isolate and map compacted heterochromatin from low cell number samples. Unexpectedly, we uncovered extensive high levels of H3K9me3-decorated, compacted heterochromatin at protein coding genes in early, uncommitted cells in the three germ layers, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type-specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed that H3K9me3 heterochromatin is required to maintain cell lineage fidelity. We propose a key role for chromatin-based restriction of gene activity via H3K9me3 during embryologic development
2018-10-31 | GSE114196 | GEO
Project description:Domains of transcriptionally repressed heterochromatin, decorated by histone 3 lysine 9 trimethylation (H3K9me3), are reduced in embryonic stem cells compared to fully differentiated cells. However, the establishment and dynamics of closed regions of chromatin at protein coding genes, in natural embryologic development, has not been described. We developed a novel, antibody-independent method to isolate and map compacted heterochromatin from low cell number samples. Unexpectedly, we uncovered extensive high levels of H3K9me3-decorated, compacted heterochromatin at protein coding genes in early, uncommitted cells in the three germ layers, undergoing profound rearrangements and reduction upon differentiation, concomitant with cell type-specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed that H3K9me3 heterochromatin is required to maintain cell lineage fidelity. We propose a key role for chromatin-based restriction of gene activity via H3K9me3 during embryologic development
2018-10-31 | GSE114195 | GEO
Project description:H3K9me3-dependent heterochromatin is considered as one of the major barriers for cell fate changes, and must be reprogrammed during fertilization to reactivate highly specialized paternal and maternal genome to establish totipotency. However, the molecular details are lacked for early embryos due to the limited materials. Here we map the genome-wide distribution of H3K9me3 modification in the early embryo as well as in the cell fate determined embryonic tissues after implantation. We find that H3K9me3 exhibits distinct dynamic features in promoters and retro-transposons. Both maternal and paternal genome undergo large scale of H3K9me3 reestablishment after fertilization, and the imbalance of maternal H3K9me3 signal over paternal last until the blastocyst stage. The rebuilding of H3K9me3 on LTR retro-transposons maintains its repression state after the global DNA demethylation, and we further discover that Chaf1a is essential for the establishment of H3K9me3 on LTRs and the loss function of Chaf1a leads to embryo development failure. Finally, we find that lineage specific H3K9me3 is established after lineage commitment in post-implantation embryos. Thus, our data demonstrate that H3K9me3-dependent heterochromatin undergoes dramatic reprogramming during early embryo development and the establishment of H3K9me3 on LTRs is essential for proper embryo development. This SuperSeries is composed of the SubSeries listed below.
2018-04-13 | GSE97778 | GEO
Project description:H3K9me3-dependent heterochromatin is considered as one of the major barriers for cell fate changes, and must be reprogrammed during fertilization to reactivate highly specialized paternal and maternal genome to establish totipotency. However, the molecular details are lacked for early embryos due to the limited materials. Here we map the genome-wide distribution of H3K9me3 modification in the early embryo as well as in the cell fate determined embryonic tissues after implantation. We find that H3K9me3 exhibits distinct dynamic features in promoters and retro-transposons. Both maternal and paternal genome undergo large scale of H3K9me3 reestablishment after fertilization, and the imbalance of maternal H3K9me3 signal over paternal last until the blastocyst stage. The rebuilding of H3K9me3 on LTR retro-transposons maintains its repression state after the global DNA demethylation, and we further discover that Chaf1a is essential for the establishment of H3K9me3 on LTRs and the loss function of Chaf1a leads to embryo development failure. Finally, we find that lineage specific H3K9me3 is established after lineage commitment in post-implantation embryos. Thus, our data demonstrate that H3K9me3-dependent heterochromatin undergoes dramatic reprogramming during early embryo development and the establishment of H3K9me3 on LTRs is essential for proper embryo development.
2018-04-13 | GSE98151 | GEO