H3S10-phosphorylation spreading in mitosis stably preserves 3D chromatin structure and functions
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PROVIDER: PRJNA1060269 | ENA |
REPOSITORIES: ENA
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Project description:Gene regulatory landscape of a cell is faithfully recapitulated in daughter cell despite widespread loss of epigenetic marks, transcription and 3D chromatin structure during cell division. How a cell remembers its gene regulatory landscape through mitosis is poorly understood. Recently, a histone modification that spreads on chromatin was postulated to be a preserver of chromatin state. Unlike most histone modifications, mitotic cells gain H3S10p but its mitotic bookmarking roles are unknown. Here, we show that as the cell loses its interphase-specific chromatin structure, spreading of H3S10p occurs throughout active chromatin domains. The level of spreading is proportional to the activity of a domain. H3S10pmarked chromatin domains are formed earlier post mitosis. Further, within the domains, promoters but not enhancers are hyper-marked by H3S10p. Using mitosis specific expression of H3S10 and its mutants (H3S10A and H3S10D), we reveal that the loss of mitotic H3S10p causes widespread opening of promoters, resulting in abrupt transcription in the next interphase. We propose that H3S10p spreading preserves the 3D-chromatin epigenetic memory where it acts as a rheostat to fine-tune gene transcription in recently divided cells.
2025-06-30 | GSE252349 | GEO
Project description:Phosphorylation of Ser10 of histone H3 (H3S10p), together with the adjacent dimethylation of Lys9 (H3K9me2), has been proposed to function as a ‘phospho-methyl switch’ to regulate mitotic chromosome dynamics and control peripheral heterochromatin localization (1, 2). Despite of immensely understanding the regulation of H3S10 phosphorylation, how this modification temporarily masks the H3K9me2 mark during mitosis is poorly understood. Herein, we report that the master mitotic kinase Plk1 phosphorylates G9a at Thr1045 (pT1045) in vitro and in vivo at early mitosis. T1045p inhibits G9a catalytic activity, leading to decrease H3K9me2 levels. RNA-sequencing analysis showed that the phospho-mimic T1045 mutant of G9a (T1045E) compromised its repressive activity on several targeted genes, which was confirmed by luciferase reporter assays. Using genome-wide epigenomic technologies, we found that T1045E mutant displayed reduced H3K9me2 level, accompanied with increased chromatin accessibility, compared to the wild-type G9a cells. Finally, we found that T1045 phosphorylation could be removed by the phosphatase PP2A at late mitosis, which inversely reactivated G9a activity on H3K9me2 level, correlated with lower levels of H3S10p. Therefore, our result may provide a mechanistic explanation for ‘phospho-methyl switch’ and highlight the importance of Plk1 and PP2A-mediated dynamic regulation of G9a during mitosis.
2023-07-17 | GSE223359 | GEO
Project description:Protein tyrosine phosphorylation is an important mechanism that regulates cytoskeleton reorganization and cell spreading of migratory cells. A number of cytoskeletal proteins are known to be tyrosine phosphorylated (pY) in different cellular processes. However, the profile of pY proteins during different stages of cell spreading has not been available.
2016-09-28 | PXD004340 | Pride
Project description:In this study we have determined the genome-wide relationship of JIL-1 kinase mediated H3S10 phosphorylation with gene expression and the distribution of the epigenetic H3K9me2 mark. We show in wild-type salivary gland cells that the H3S10ph mark is predominantly enriched at active genes whereas the H3K9me2 mark largely is associated with inactive genes.
2014-02-12 | GSE54438 | GEO
Project description:Domains of heterochromatin play important roles in the maintenance and regulation of eukaryotic genomes. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates the existence of robust mechanisms that limit heterochromatin spreading and thereby avoid silencing of expressed genes. A number of specific sequence elements have been found to serve as barriers to heterochromatin spreading; however, the mechanisms by which spreading is curtailed are generally not well understood. Here we uncover a role for PAF complex component Leo1 in regulating heterochromatin cis-spreading. A genetic screen revealed that loss of Leo1 results in spreading of heterochromatin across a centromeric (IRC) boundary element in fission yeast. Similar heterochromatin spreading was seen upon deletion of other components of the PAF complex, but not other factors involved in transcription-coupled chromatin modification, indicating a specific role for the PAF complex in heterochromatin regulation. Loss of Leo1 is associated with reduced levels of H4K16 acetylation at the boundary, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1? cells, suggesting that Leo1 antagonises heterochromatin spreading by facilitating H4K16 acetylation. Interestingly, Leo1 also regulates heterochromatin spreading independently of boundaries, and loss of Leo1 causes redistribution of heterochromatin, in particular resulting in substantial expansion of telomeric heterochromatin domains. The PAF complex is known to be an important regulator of transcription-related chromatin modifications; our findings reveal a previously undescribed role for this complex in global regulation of heterochromatin spreading in cis. 8 samples: input (whole cell extract) and IP from H3K9me2 ChIP in wild-type and leo1? cells, in duplicate
2015-05-22 | E-GEOD-61688 | biostudies-arrayexpress
Project description:We use small RNA sequencing to look for spreading of secondary and tertiary siRNAs along transcripts targeted by ectopic hairpin-derived primary siRNAs. We find that signals within the 3' UTR inhibit siRNA spreading. sequencing of 20-30nt sRNAs from Argonaute immunoprecipitation
2013-12-26 | E-GEOD-52534 | biostudies-arrayexpress
Project description:Pervasive phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora B/C plays an important role in mitosis; however, this mark has also been observed at specific genic promoters and enhancers in interphase, implicating mitosis-independent functions. Using the FUCCI cell cycle reporter, we found that 30% of the genome is persistently marked with H3S10ph in interphase mouse embryonic stem cells (ESCs). H3S10ph demarcates broad gene-rich euchromatic regions in G1 and shows remarkable correlation with domains of early DNA replication timing (RT). Consistent with mitosis-independent H3S10 kinase activity, this pattern was preserved in ESCs treated with hesperidin, a potent inhibitor of Aurora B/C. Disruption of H3S10ph by expression of non-phosphorylatable H3.3S10A results in ectopic spreading of H3K9me2 into adjacent H3S10ph-enriched euchromatic regions, mimicking the phenotype observed in Drosophila JIL-1 kinase mutants. Conversely, H3S10ph domains expand in interphase Glp-/- ESCs, revealing that H3S10ph expansion is restricted by H3K9me2. Strikingly, spreading of H3S10ph at RT transition regions (TTRs) is accompanied by aberrant strand-biased transcription initiation of genes and repetitive elements co-oriented with the replication fork, indicating that H3K9me2 plays a critical role in establishing repressive chromatin on the leading strand. Finally, we show that H3S10ph is also present in interphase murine embryonic fibroblasts (MEFs), but is restricted to intragenic regions of actively transcribing genes. Our study provides a detailed map of interphase H3S10ph in ESCs and MEFs, uncovering a previously unappreciated crosstalk between the opposing marks H3S10ph and H3K9me2, and a role for the latter in ensuring appropriate transcription at TTRs in ESCs.
2017-11-20 | GSE97947 | GEO
Project description:Domains of heterochromatin play important roles in the maintenance and regulation of eukaryotic genomes. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates the existence of robust mechanisms that limit heterochromatin spreading and thereby avoid silencing of expressed genes. A number of specific sequence elements have been found to serve as barriers to heterochromatin spreading; however, the mechanisms by which spreading is curtailed are generally not well understood. Here we uncover a role for PAF complex component Leo1 in regulating heterochromatin cis-spreading. A genetic screen revealed that loss of Leo1 results in spreading of heterochromatin across a centromeric (IRC) boundary element in fission yeast. Similar heterochromatin spreading was seen upon deletion of other components of the PAF complex, but not other factors involved in transcription-coupled chromatin modification, indicating a specific role for the PAF complex in heterochromatin regulation. Loss of Leo1 is associated with reduced levels of H4K16 acetylation at the boundary, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1Δ cells, suggesting that Leo1 antagonises heterochromatin spreading by facilitating H4K16 acetylation. Interestingly, Leo1 also regulates heterochromatin spreading independently of boundaries, and loss of Leo1 causes redistribution of heterochromatin, in particular resulting in substantial expansion of telomeric heterochromatin domains. The PAF complex is known to be an important regulator of transcription-related chromatin modifications; our findings reveal a previously undescribed role for this complex in global regulation of heterochromatin spreading in cis.
2015-05-22 | GSE61688 | GEO
Project description:We report genome wide mapping of the histone variant H2A.Z during G0/G1 and mitosis in T24 bladder cancer cells. The results show that the broad enrichment pattern of H2A.Z near transcription start sites of active genes is maintained during mitosis. Furthermore, using H2A.Z localization to visualize nucleosome positioning near the start site, we see that the +1 nucleosome of active genes shifts upstream to occupy the transcription start sites during mitosis and the nucleosome depleted region is shortened. H2A.Z is also maintained on the -2 nucleosome which also shifts towrds the transcription start site during mitosis, further contributing to the shorteneing of the nucleosome depleted region. Examination of H2A.Z duing G0/G1 and mitosis in bladder cancer cells
2010-06-24 | E-GEOD-19568 | biostudies-arrayexpress
Project description:Entry into and exit from mitosis is driven by precisely-timed changes in protein abundance, and involves transcriptional regulation and protein degradation. However, the role of translational regulation in modulating cellular protein content during mitosis remains poorly understood. Here, using ribosome profiling, we show that translational, rather than transcriptional regulation is the dominant mechanism for modulating protein synthesis at mitotic entry. The vast majority of regulated mRNAs are translationally repressed, which contrasts previous findings of selective mRNA translational activation at mitotic entry. One of the most pronounced translationally repressed genes in mitosis is Emi1, an inhibitor of the anaphase promoting complex (APC), which is degraded during mitosis. We show that Emi1 degradation is insufficient for full APC activation and that simultaneous translational repression is required. These results provide a genome-wide view of protein translation during mitosis and suggest that translational repression may be used to ensure complete protein inactivation Ribosome profiling and mRNA-seq from 3 time points in the cell cycle
2015-09-01 | E-GEOD-67902 | biostudies-arrayexpress