Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214383 | GEO | 2023/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

Project description:The roles of neurogenic pioneer transcription factors and chromatin remodelers have been characterized in that process in developing animal models and cancers. However how these factors interact with each other to regulate cell state transitions in human neurogenesis remains unclear. Here we investigated the activity of the pioneer proneural factor ASCL1 in an in vitro model of human neurogenesis. We found that ASCL1 expression characterizes a transitional state from cycling neural progenitor to post-mitotic neuron, and ASCL1 knockout impedes progenitor neuronal differentiation. ASCL1 binds to genomic targets to regulate loci promoting differentiation by different mechanisms. Acting as a classical pioneer transcription factor, its binding to compacted chromatin is required to induce transcriptional activity. At other loci, it acts as a non-pioneer chromatin remodeler, accessing permissive chromatin to further increase chromatin accessibility. We show that ASCL1 interacts with ATPase-active BAF mSWI/SNF chromatin remodelers at cis-regulatory elements, altering the chromatin regulatory landscape at a subset of target genes. This cooperative function is predominant at sites of non-pioneer chromatin remodeler function where ASCL1 requires mSWI/SNF for DNA binding while ASCL1 classical pioneer activity does not involve significant mSWI/SNF binding. Our work establishes novel roles for ASCL1 and for an interaction with mSWI/SNF in regulating epigenetic states in human neurogenesis.

2023-03-14 | GSE214700 | GEO

Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP1 shapes 3D enhancer landscapes [SWI_SNF_complex]

Project description:The mechanism controlling the dynamic targeting of SWI/SNF has long been postulated to be coordinated by transcription factors (TFs), yet identifying and demonstrating the influence of different TFs has proven difficult. In this study we take a multi-omics approach to directly interrogate transient SWI/SNF interactors, chromatin targeting, and the plasticity of the resulting 3D epigenetic landscape. We utilized the novel proximity based labeling technique TurboID to identify the AP1 family as a critical interacting partner for endogenous SWI/SNF complexes. Validation through CUT&RUN profiling demonstrated SWI/SNF targeting enrichment at AP1 bound loci, and SWI/SNF – AP1 cooperation in chromatin targeting. Mapping of 3D chromatin structure via HiChIP revealed AP1-SWI/SNF dependent restructuring of promoter-enhancer architecture and generation of enhancer hubs, ultimately regulating transcription. Through direct interrogation of the SWI/SNF – AP1 interaction, we demonstrate a SWI/SNF functional dependency on AP1 mediated chromatin localization. We propose that pioneer factors such as AP1 bind and target SWI/SNF to inactive chromatin, where it restructures the genomic landscape into an active state through epigenetic rewiring spanning multiple dimensions.

2022-10-17 | GSE175532 | GEO

Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP1 shapes 3D enhancer landscapes [RNA-Seq]

2022-10-17 | GSE175531 | GEO

Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP1 shapes 3D enhancer landscapes [AP_1 family]

2022-10-15 | GSE196955 | GEO

Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP1 shapes 3D enhancer landscapes [Histone_modification]

2022-10-17 | GSE175530 | GEO