Similar Datasets
Project description:H3K9me3-heterochromatin, compacted by HP1 proteins, restricts transcription factor binding and functions as a barrier to cell fate changes in development and reprogramming1,2. To investigate principles underlying H3K9me3-heterochromatin maintenance in mammalian cells, we applied degron engineering3,4 on mouse ESCs to conditionally deplete all three H3K9me3-methyltransferases within one hour and found an unexpectedly dynamic nature of heterochromatin maintenance. Following H3K9me3 methyltransferases degradation, HP1β dissociates from heterochromatin within three hours, and transcription factors quickly access the de-compacted heterochromatin, activating transcription of their targets, which then promotes H3K9me3 decay. Both passive dilution and active removal contribute to the H3K9me3 decay. Mathematical modeling reveals distinct H3K9me3 heterochromatin states with diverse chromatin features which influence initial H3K9me3 levels and the stability of H3K9me3 domains, thereby expanding our understanding of distinct heterochromatin domains. Rampant transposable element de-repression interferes with transcription of poised early developmental and signaling genes outside H3K9me3-domains, highlighting the intricate roles of dynamic H3K9me3-heterochromatin maintenance in safeguarding developmental programs. Our findings deconvolve the hierarchical relationships between H3K9me3 marks, methyltransferases, HP1 and transcription factors to reveal principles of H3K9me3-heterochromatin maintenance and how its remodeling enables transcription and cell fate change.
2024-09-19 | GSE233040 | GEO
Project description:H3K9me3-heterochromatin, compacted by HP1 proteins, restricts transcription factor binding and functions as a barrier to cell fate changes in development and reprogramming1,2. To investigate principles underlying H3K9me3-heterochromatin maintenance in mammalian cells, we applied degron engineering3,4 on mouse ESCs to conditionally deplete all three H3K9me3-methyltransferases within one hour and found an unexpectedly dynamic nature of heterochromatin maintenance. Following H3K9me3 methyltransferases degradation, HP1β dissociates from heterochromatin within three hours, and transcription factors quickly access the de-compacted heterochromatin, activating transcription of their targets, which then promotes H3K9me3 decay. Both passive dilution and active removal contribute to the H3K9me3 decay. Mathematical modeling reveals distinct H3K9me3 heterochromatin states with diverse chromatin features which influence initial H3K9me3 levels and the stability of H3K9me3 domains, thereby expanding our understanding of distinct heterochromatin domains. Rampant transposable element de-repression interferes with transcription of poised early developmental and signaling genes outside H3K9me3-domains, highlighting the intricate roles of dynamic H3K9me3-heterochromatin maintenance in safeguarding developmental programs. Our findings deconvolve the hierarchical relationships between H3K9me3 marks, methyltransferases, HP1 and transcription factors to reveal principles of H3K9me3-heterochromatin maintenance and how its remodeling enables transcription and cell fate change.
2024-09-19 | GSE233039 | GEO
Project description:H3K9me3-heterochromatin, compacted by HP1 proteins, restricts transcription factor binding and functions as a barrier to cell fate changes in development and reprogramming1,2. To investigate principles underlying H3K9me3-heterochromatin maintenance in mammalian cells, we applied degron engineering3,4 on mouse ESCs to conditionally deplete all three H3K9me3-methyltransferases within one hour and found an unexpectedly dynamic nature of heterochromatin maintenance. Following H3K9me3 methyltransferases degradation, HP1β dissociates from heterochromatin within three hours, and transcription factors quickly access the de-compacted heterochromatin, activating transcription of their targets, which then promotes H3K9me3 decay. Both passive dilution and active removal contribute to the H3K9me3 decay. Mathematical modeling reveals distinct H3K9me3 heterochromatin states with diverse chromatin features which influence initial H3K9me3 levels and the stability of H3K9me3 domains, thereby expanding our understanding of distinct heterochromatin domains. Rampant transposable element de-repression interferes with transcription of poised early developmental and signaling genes outside H3K9me3-domains, highlighting the intricate roles of dynamic H3K9me3-heterochromatin maintenance in safeguarding developmental programs. Our findings deconvolve the hierarchical relationships between H3K9me3 marks, methyltransferases, HP1 and transcription factors to reveal principles of H3K9me3-heterochromatin maintenance and how its remodeling enables transcription and cell fate change.
2024-09-19 | GSE231845 | GEO
Project description:H3K9me3-heterochromatin, compacted by HP1 proteins, restricts transcription factor binding and functions as a barrier to cell fate changes in development and reprogramming1,2. To investigate principles underlying H3K9me3-heterochromatin maintenance in mammalian cells, we applied degron engineering3,4 on mouse ESCs to conditionally deplete all three H3K9me3-methyltransferases within one hour and found an unexpectedly dynamic nature of heterochromatin maintenance. Following H3K9me3 methyltransferases degradation, HP1β dissociates from heterochromatin within three hours, and transcription factors quickly access the de-compacted heterochromatin, activating transcription of their targets, which then promotes H3K9me3 decay. Both passive dilution and active removal contribute to the H3K9me3 decay. Mathematical modeling reveals distinct H3K9me3 heterochromatin states with diverse chromatin features which influence initial H3K9me3 levels and the stability of H3K9me3 domains, thereby expanding our understanding of distinct heterochromatin domains. Rampant transposable element de-repression interferes with transcription of poised early developmental and signaling genes outside H3K9me3-domains, highlighting the intricate roles of dynamic H3K9me3-heterochromatin maintenance in safeguarding developmental programs. Our findings deconvolve the hierarchical relationships between H3K9me3 marks, methyltransferases, HP1 and transcription factors to reveal principles of H3K9me3-heterochromatin maintenance and how its remodeling enables transcription and cell fate change.
2024-09-19 | GSE270213 | GEO
Project description:H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1?, HP1? and HP1? These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1? and HP1?. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription.
| S-EPMC3022755 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-06 | E-GEOD-48987 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-11-06 | GSE48987 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-12-10 | E-GEOD-70083 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-10-31 | GSE208296 | GEO
Project description:HP1 family proteins are adaptor molecules, containing two related chromo domains that are required for chromatin packaging and gene silencing. Here we present the structure of the chromo shadow domain from mouse HP1beta bound to a peptide containing a consensus PXVXL motif found in many HP1 binding partners. The shadow domain exhibits a novel mode of peptide recognition, where the peptide binds across the dimer interface, sandwiched in a beta-sheet between strands from each monomer. The structure allows us to predict which other shadow domains bind similar PXVXL motif-containing peptides and provides a framework for predicting the sequence specificity of the others. We show that targeting of HP1beta to heterochromatin requires shadow domain interactions with PXVXL-containing proteins in addition to chromo domain recognition of Lys-9-methylated histone H3. Interestingly, it also appears to require the simultaneous recognition of two Lys-9-methylated histone H3 molecules. This finding implies a further complexity to the histone code for regulation of chromatin structure and suggests how binding of HP1 family proteins may lead to its condensation.
| S-EPMC1271814 | biostudies-literature