Genomic and proteomic resolution of heterochromatin and its restriction of alternate fate genes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343263 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4253040.fastq.gz | Fastqsanger.gz | |||
| SRR4253050.fastq.gz | Fastqsanger.gz | |||
| SRR4253041.fastq.gz | Fastqsanger.gz | |||
| SRR4253051.fastq.gz | Fastqsanger.gz | |||
| SRR4253042.fastq.gz | Fastqsanger.gz |
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Project description:Heterochromatic regions in mammalian cells suppress recombination, silence transcription, and are crucial for maintaining cell differentiation. Genomic and biochemical characterization of heterochromatin has relied on the associated histone modifications H3K9me3 and H3K27me3, yet these marks are also found in euchromatic regions that permit transcription. We employed a biophysical method to isolate sonication resistant heterochromatin from human somatic cells, mapped its genomic organization compared to histone modifications, and used proteomics to reveal an extensive number of heterochromatin-bound proteins. We discriminate subtypes of H3K9me3- and H3K27me3-marked domains, in sonication-resistant heterochromatin versus euchromatin, and we present a resource of hundreds of proteins that preferentially bind heterochromatin, a set enriched for RNA-binding proteins and proteins that oppose iPS reprogramming. The sonication-resistant heterochromatin landscape includes repressed genes for alternative lineages that are resistant to activation by introduced transcription factors. Depletion of identified heterochromatin-associated proteins reduces this barrier, rendering alternative-lineage genes more competent for transcriptional activation.
2017-12-21 | GSE87040 | GEO
Project description:Heterochromatic regions in mammalian cells suppress recombination, silence transcription, and are crucial for maintaining cell differentiation. Genomic and biochemical characterization of heterochromatin has relied on the associated histone modifications H3K9me3 and H3K27me3, yet these marks are also found in euchromatic regions that permit transcription. We employed a biophysical method to isolate sonication resistant heterochromatin from human somatic cells, mapped its genomic organization compared to histone modifications, and used proteomics to reveal an extensive number of heterochromatin-bound proteins. We discriminate subtypes of H3K9me3- and H3K27me3-marked domains, in sonication-resistant heterochromatin versus euchromatin, and we present a resource of hundreds of proteins that preferentially bind heterochromatin, a set enriched for RNA-binding proteins and proteins that oppose iPS reprogramming. The sonication-resistant heterochromatin landscape includes repressed genes for alternative lineages that are resistant to activation by introduced transcription factors. Depletion of identified heterochromatin-associated proteins reduces this barrier, rendering alternative-lineage genes more competent for transcriptional activation.
2017-12-21 | GSE87039 | GEO
Project description:Heterochromatin is integral to cell identity maintenance by impeding the activation of genes for alternate cell fates. Heterochromatic regions are associated with histone 3 lysine 9 trimethylation (H3K9me3) or H3K27me3, but these modifications are also found in euchromatic regions that permit transcription. We discovered that resistance to sonication is a reliable indicator of the heterochromatin state, and we developed a biophysical method (gradient-seq) to discriminate subtypes of H3K9me3 and H3K27me3 domains in sonication-resistant heterochromatin (srHC) versus euchromatin. These classifications are more accurate than the histone marks alone in predicting transcriptional silence and resistance of alternate fate genes to activation during direct cell conversion. Our proteomics of H3K9me3-marked srHC and functional screens revealed diverse proteins, including RBMX and RBMXL1, that impede gene induction during cellular reprogramming. Isolation of srHC with gradient-seq provides a genome-wide map of chromatin structure, elucidating subtypes of repressed domains that are uniquely predictive of diverse other chromatin properties.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2017-12-21 | GSE87041 | GEO
Project description:Genomic and proteomic resolution of heterochromatin and its restriction of alternate fate genes (ChIP-seq)
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Project description:Genomic and proteomic resolution of heterochromatin and its restriction of alternate fate genes (RNA-seq)
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Project description:DNA methylation at 5-position of cytosine (5mC) is one of the best studied epigenetic modifications that plays important roles in diverse biological processes. Iterative oxidation of 5mC by the Ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), which can be further processed by DNA repair proteins leading to DNA demethylation. Functional characterization of the Tet proteins has been complicated by the redundancy between the three Tet proteins. Using the CRISPR/Cas9 technology, we have generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (TKO). Whole genome bisulphite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs distal enhancers as well as promoters that significantly overlap with 5hmC, 5fC and 5caC. Characterization of the Tet TKO ESCs revealed a function for Tet proteins in cell fate restriction as Tet TKO ESCs tend to adopt both primed pluripotent stem cell-like state and 2-cell embryo-like state. In addition, Tet TKO ESCs exhibit elongated telomeres. Thus, our study reveals a role of Tet proteins not only in DNA demethylation, but also in cell fate restriction and telomere maintenance. 2 samples for WGBS and 2 samples for RNA-seq
2014-09-22 | E-GEOD-56986 | biostudies-arrayexpress
Project description:Astrocytes within specific brain regions contribute uniquely to regional circuits for higher-order brain function through interactions with local neurons. The regional diversification of astrocytes is dictated by their embryonic origin, yet the mechanisms governing their regional allocation remain unknown. Here we show that allocation of astrocytes to specific brain regions requires the transcription factor 4 (Tcf4) mediated fate restriction during brain development. Loss of Tcf4 in ventral telencephalic neural progenitors alters the fate of oligodendrocyte precursors to transient intermediate astrocyte precursor cells, resulting in mislocated astrocytes in the dorsal neocortex. These ectopic astrocytes originated from the ventral telencephalon engage with neurons and acquire features reminiscent of local neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during differentiation of oligodendrocyte precursors, thereby restricting the fate to oligodendrocyte lineage. Our study reveals that fate restriction governs regional astrocyte allocation, contributing to astrocyte diversification across brain regions.
2024-08-14 | GSE244709 | GEO
Project description:Resolution and formation of facultative heterochromatin is essential to development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood due to difficulty with interrogating heterochromatin dynamics and structure in vivo. BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are known to promote chromatin accessibility. As the function of topoisomerase IIa (TOP2A) is largely dependent on BAF complexes in embryonic stem (ES) cells, we tested whether TOP2 was involved in BAF-mediated resolution of heterochromatin by performing ATAC-seq on ES cells treated with the TOP2 inhibitor ICRF-193, Brg1 (the primary ATPase subunit of esBAF complexes) conditional knockout cells, and Baf53a (a non-catalytic subunit dispensable for in vitro remodeling) conditional knockout cells. We found that TOP2 synergizes with BAF complexes genome-wide to resolve facultative heterochromatin to accessible chromatin at a large number of regulatory elements.
2017-03-01 | GSE94039 | GEO
Project description:DNA methylation at 5-position of cytosine (5mC) is one of the best studied epigenetic modifications that plays important roles in diverse biological processes. Iterative oxidation of 5mC by the Ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), which can be further processed by DNA repair proteins leading to DNA demethylation. Functional characterization of the Tet proteins has been complicated by the redundancy between the three Tet proteins. Using the CRISPR/Cas9 technology, we have generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (TKO). Whole genome bisulphite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs distal enhancers as well as promoters that significantly overlap with 5hmC, 5fC and 5caC. Characterization of the Tet TKO ESCs revealed a function for Tet proteins in cell fate restriction as Tet TKO ESCs tend to adopt both primed pluripotent stem cell-like state and 2-cell embryo-like state. In addition, Tet TKO ESCs exhibit elongated telomeres. Thus, our study reveals a role of Tet proteins not only in DNA demethylation, but also in cell fate restriction and telomere maintenance.
2014-09-22 | GSE56986 | GEO