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OCT4 cooperates with distinct chromatin remodelers in naive and primed pluripotent states in human [ChIP-Seq]

ABSTRACT: Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). We mapped the protein-protein interactions of OCT4 in naive and primed hESCs, revealing extensive connections to ATP-dependent nucleosome remodeling complexes. In naive hESCs, OCT4 is associated with both BRG1 and BRM, the two mutually exclusive ATPase subunits of the BAF complex. Genome-wide location analyses and genetic deletion studies reveal that these two enzymes exert a functionally redundant role in transcriptional regulation of blastocyst-specific genes. In contrast, OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage-associated genes in primed hESCs. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential compositions of the BAF complex in controlling distinct transcriptional programs governing naive vs. primed human pluripotent states.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147716 | GEO | 2021/07/01

REPOSITORIES: GEO

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OCT4 cooperates with distinct chromatin remodelers in naive and primed pluripotent states in human [RNA-Seq]

Project description:Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). We mapped the protein-protein interactions of OCT4 in naive and primed hESCs, revealing extensive connections to ATP-dependent nucleosome remodeling complexes. In naive hESCs, OCT4 is associated with both BRG1 and BRM, the two mutually exclusive ATPase subunits of the BAF complex. Genome-wide location analyses and genetic deletion studies reveal that these two enzymes exert a functionally redundant role in transcriptional regulation of blastocyst-specific genes. In contrast, OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage-associated genes in primed hESCs. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential compositions of the BAF complex in controlling distinct transcriptional programs governing naive vs. primed human pluripotent states.

2021-07-01 | GSE147750 | GEO

Oct4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human [RNA-seq}

Project description:Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their physical interactome in human ESCs (hESCs) has not been explored thus far. Here we mapped the protein-protein interactions of OCT4 in naive and primed hESCs, revealing extensive connections to ATP-dependent nucleosome remodeling complexes. In naive hESCs, OCT4 is associated with both BRG1 and BRM, the two core ATPases of the BAF complex. Genome-wide location analyses and genetic deletion studies reveal that these two enzymes exert a functionally redundant role in transcriptional regulation of blastocyst-specific genes. In contrast, in primed hESCs OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage associted genes. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential BAF complex composition to control distinct transcriptional programs in naive and primed hESCs.

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Oct4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human [CUT&Tag]

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OCT4 IP-MS in Naive and Primed Human ESCs

2021-09-12 | PXD026556 | Pride

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BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

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2018-11-29 | GSE75568 | GEO

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2021-11-03 | PXD026638 | Pride

Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Project description:Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation immunopurification with mass spectrometry we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocytes (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60, and BAF170 modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific enhancers. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

2019-11-13 | PXD012721 | Pride

OCT4 cooperates with distinct chromatin remodelers in naive and primed pluripotent states in human

Project description:OCT4 cooperates with distinct chromatin remodelers in naive and primed pluripotent states in human

| PRJNA616308 | ENA