ZNF695 Represses Hepatic Genes and Regulates H3K9me3-Heterochromatin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA859144 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19867322_1.fastq.gz | Fastqsanger.gz | |||
| SRR19867322_2.fastq.gz | Fastqsanger.gz | |||
| SRR19867323_1.fastq.gz | Fastqsanger.gz | |||
| SRR19867323_2.fastq.gz | Fastqsanger.gz | |||
| SRR19867324_1.fastq.gz | Fastqsanger.gz |
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Project description:ZNF695 Represses Hepatic Genes and Regulates H3K9me3-Heterochromatin [RNA-seq]
| PRJNA859145 | ENA
Project description:ZNF695 Represses Hepatic Genes and Regulates H3K9me3-Heterochromatin [CUT&RUN]
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Project description:In any cell type, repetitive elements and alternative lineage genes can be silenced by heterochromatin marked by H3K9me3 and/or H3K27me3. During cellular reprogramming to pluripotency and to liver, genes marked by H3K9me3 are the most difficult to activate. Given that KRAB domain-containing, zinc finger proteins (KRAB-ZFPs) can direct repressive H3K9me3 at genes and transposable elements, we sought to identify KRAB-ZFPs that silence liver genes in non-liver lineages and could be useful for down-regulating during human fibroblast to hepatocyte (hiHep) reprogramming. We identified six KRAB-ZFPs that are essentially not expressed in liver or BJ fibroblasts, but are expressed in many other tissues. We knocked down each KRAB-ZFP during hepatic reprogramming of human fibroblasts and found that only knockdown of primate-specific ZNF695 allowed hundreds of hepatic genes in H3K9me3-heterochromatin to be derepressed. ZNF695 localizes primarily at LINE repeat elements and at gene introns that were linked to gene expression changes. ZNF695 exhibits nuclear mobility characteristics similar to well-characterized heterochromatin proteins. While most KRAB-ZFPs tested that exhibit diminution in one tissue (liver) did not functionally repress that tissue’s genes in another cell type, our strategy revealed a KRAB-ZFP that can be targeted to allow H3K9me3-heterochromatic genes to be derepressed during cellular reprogramming.
2024-10-31 | GSE208295 | GEO
Project description:In any cell type, repetitive elements and alternative lineage genes can be silenced by heterochromatin marked by H3K9me3 and/or H3K27me3. During cellular reprogramming to pluripotency and to liver, genes marked by H3K9me3 are the most difficult to activate. Given that KRAB domain-containing, zinc finger proteins (KRAB-ZFPs) can direct repressive H3K9me3 at genes and transposable elements, we sought to identify KRAB-ZFPs that silence liver genes in non-liver lineages and could be useful for down-regulating during human fibroblast to hepatocyte (hiHep) reprogramming. We identified six KRAB-ZFPs that are essentially not expressed in liver or BJ fibroblasts, but are expressed in many other tissues. We knocked down each KRAB-ZFP during hepatic reprogramming of human fibroblasts and found that only knockdown of primate-specific ZNF695 allowed hundreds of hepatic genes in H3K9me3-heterochromatin to be derepressed. ZNF695 localizes primarily at LINE repeat elements and at gene introns that were linked to gene expression changes. ZNF695 exhibits nuclear mobility characteristics similar to well-characterized heterochromatin proteins. While most KRAB-ZFPs tested that exhibit diminution in one tissue (liver) did not functionally repress that tissue’s genes in another cell type, our strategy revealed a KRAB-ZFP that can be targeted to allow H3K9me3-heterochromatic genes to be derepressed during cellular reprogramming.
2024-10-31 | GSE207017 | 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 | GSE233040 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-10-31 | GSE208296 | 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:Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. Here we explore whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems; orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1, and strains deficient for any exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains dispersed across the genome. Heterochromatin establishment outside of canonical domains in Neurospora share the unusual characteristic of DNA methylation-dependent H3K9me3; typically, H3K9me3 establishment is independent of DNA methylation. Consistent with this, the hyper-H3K9me3 phenotype of LSD1 knock-out strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.
2021-07-21 | PXD017300 | Pride