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BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

ABSTRACT: Chromatin remodeling molecules of the BAF complex, Brg1 and Baf155, as well as other chromatin remodeling modeling molecules have been described to enhance Oct4, Sox2, Klf4 and c-Myc mediated reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs). Brg1 maintains pluripotency of mouse embryonic stem cells (mESCs) by modulating the expression of pluripotency genes including Oct4 in synergism with LIF/STAT signaling. Interestingly, unlike mESCs, BAF complex in human embryonic stem cells (hESCs) is composed of both BAF155 and BAF170, where BAF170 plays a role in maintaining hESCs pluripotency. In this study, we describe that BRG1 and BAF155 enhance reprogramming of adult human fibroblasts. Overexpression of BAF155 does not affect pluripotency of hiPSCs as tested by global gene expression profiling as well as in vivo and in vitro assays. Additionally, these findings show that BRG1 and BAF155 expression can enhance reprogramming even in the absence of LIF/STAT signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75568 | GEO | 2018/11/29

REPOSITORIES: GEO

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

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2019-11-13 | PXD012721 | Pride

Chromatin regulation by BAF170 controls cerebral cortical size and thickness.

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2020-11-17 | GSE144243 | GEO

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

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

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

2021-07-02 | GSE167988 | 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

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