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Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

ABSTRACT: We interfeered with the ASCL1-mSWI/SNF interaction: to abolish ASCL1 function, we knocked out ASCL1 in human iPSCs, while we used the BRM014 inhibitor to block the mSWI/SNF ATPase activity. We performed ATACseq in WT, ASCL1 KO, and BRM014-treated cells at DIV24, when ASCL1 expression is highest during neural differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214380 | GEO | 2023/03/14

REPOSITORIES: GEO

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Identifying the genomic regions co-bound by ASCL1 and mSWI/SNF remodelers during neural differentiation [ChIP-seq]

Project description:We interfeered with the ASCL1-mSWI/SNF interaction: to abolish ASCL1 function, we knocked out ASCL1 in human iPSCs, while we used the BRM014 inhibitor to block the mSWI/SNF ATPase activity. We then performed ASCL1 ChIPseq in DIV24 WT and BRM014-treated neural cultures, and SMARCB1 ChIPseq in DIV24 WT and ASCL1 KO neural cultures, when ASCL1 expression is highest.

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Identifying the genomic regions co-bound by ASCL1 and mSWI/SNF remodelers during neural differentiation [ChIP-seq]

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Single cell transcriptomes of neurally differentiated wildtype and ASCL1-KO human iPSCs, in the presence of NOTCH inhibitor DAPT [scRNA-seq]

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Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

Project description:Identifying the genomic regions where ASCL1 and mSWI/SNF remodelers are both required to regulate chromatin accessibility during neural differentiation [ATAC-seq]

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Identifying the transcriptional output associated with distal regulatory elements where ASCL1 interacts with mSWI/SNF remodelers to regulate neural differentiation [RNA-seq]

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Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression, though mechanisms through which pioneer transcription factors remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that endogenous expression of neurogenic transcription factor ASCL1, considered a classical pioneer factor, defines a transient population of progenitors in human neural differentiation. Testing ASCL1’s pioneer function using a knockout model to define the unbound state, we found that endogenous expression of ASCL1 drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a nonpioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. ASCL1 interacts with BAF SWI/SNF chromatin remodeling complexes, primarily at targets where it acts as a nonpioneer factor, and we provide evidence for codependent DNA binding and remodeling at a subset of ASCL1 and SWI/SNF cotargets. Our findings provide new insights into ASCL1 function regulating activation of long-range regulatory elements in human neurogenesis and uncover a novel mechanism of its chromatin remodeling function codependent on partner ATPase activity.

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Project description:Pioneer factor ASCL1 cooperates with the mSWI/SNF complex at distal regulatory elements to regulate human neural differentiation

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