ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation

Cristina Dias; Oana Paun; Yu Xuan Tan; Harshil Patel; Clementina Cobolli-Gigli; Francois Guillemot

doi:10.1101/2022.10.09.510609

ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation

Cristina Dias^*, Oana Paun, Yu Xuan Tan, Harshil Patel, Clementina Cobolli-Gigli, Francois Guillemot

^*Corresponding author for this work

Research output: Working paper/Preprint › Preprint

Abstract

Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression. The role of neurogenic pioneer factor ASCL1 in shaping chromatin landscape in human neurogenesis remains unclear. Here we show that ASCL1 acts as a pioneer transcription factor in a transient population of progenitors. Using an in vitro ASCL1 knockout model we show it drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a non-pioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. We find ASCL1 directly interacts with mammalian BAF SWI/SNF chromatin remodeling complexes, essential for neurogenesis and involved in multiple neurodevelopmental disorders. ASCL1 acts as a non-pioneer chromatin remodeler to regulate gene expression at a subset of loci, requiring mBAF SWI/SNF’s ATPase activity for cis-regulation of gene expression. Our findings demonstrate that ASCL1 is a key chromatin remodeler in human neurogenesis, uncovering an alternative mechanism of remodeling function dependent on partner ATPase activity.

Original language	English
Publisher	bioRxiv
DOIs	https://doi.org/10.1101/2022.10.09.510609
Publication status	Published - 9 Oct 2022

Access to Document

10.1101/2022.10.09.510609Licence: CC BY-NC-ND

Cite this

@techreport{624db8a4600a460592c2634be526284b,

title = "ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation",

abstract = "Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression. The role of neurogenic pioneer factor ASCL1 in shaping chromatin landscape in human neurogenesis remains unclear. Here we show that ASCL1 acts as a pioneer transcription factor in a transient population of progenitors. Using an in vitro ASCL1 knockout model we show it drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a non-pioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. We find ASCL1 directly interacts with mammalian BAF SWI/SNF chromatin remodeling complexes, essential for neurogenesis and involved in multiple neurodevelopmental disorders. ASCL1 acts as a non-pioneer chromatin remodeler to regulate gene expression at a subset of loci, requiring mBAF SWI/SNF{\textquoteright}s ATPase activity for cis-regulation of gene expression. Our findings demonstrate that ASCL1 is a key chromatin remodeler in human neurogenesis, uncovering an alternative mechanism of remodeling function dependent on partner ATPase activity.",

author = "Cristina Dias and Oana Paun and Tan, {Yu Xuan} and Harshil Patel and Clementina Cobolli-Gigli and Francois Guillemot",

year = "2022",

month = oct,

day = "9",

doi = "10.1101/2022.10.09.510609",

language = "English",

publisher = "bioRxiv",

type = "WorkingPaper",

institution = "bioRxiv",

}

TY - UNPB

T1 - ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation

AU - Dias, Cristina

AU - Paun, Oana

AU - Tan, Yu Xuan

AU - Patel, Harshil

AU - Cobolli-Gigli, Clementina

AU - Guillemot, Francois

PY - 2022/10/9

Y1 - 2022/10/9

N2 - Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression. The role of neurogenic pioneer factor ASCL1 in shaping chromatin landscape in human neurogenesis remains unclear. Here we show that ASCL1 acts as a pioneer transcription factor in a transient population of progenitors. Using an in vitro ASCL1 knockout model we show it drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a non-pioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. We find ASCL1 directly interacts with mammalian BAF SWI/SNF chromatin remodeling complexes, essential for neurogenesis and involved in multiple neurodevelopmental disorders. ASCL1 acts as a non-pioneer chromatin remodeler to regulate gene expression at a subset of loci, requiring mBAF SWI/SNF’s ATPase activity for cis-regulation of gene expression. Our findings demonstrate that ASCL1 is a key chromatin remodeler in human neurogenesis, uncovering an alternative mechanism of remodeling function dependent on partner ATPase activity.

AB - Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression. The role of neurogenic pioneer factor ASCL1 in shaping chromatin landscape in human neurogenesis remains unclear. Here we show that ASCL1 acts as a pioneer transcription factor in a transient population of progenitors. Using an in vitro ASCL1 knockout model we show it drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a non-pioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. We find ASCL1 directly interacts with mammalian BAF SWI/SNF chromatin remodeling complexes, essential for neurogenesis and involved in multiple neurodevelopmental disorders. ASCL1 acts as a non-pioneer chromatin remodeler to regulate gene expression at a subset of loci, requiring mBAF SWI/SNF’s ATPase activity for cis-regulation of gene expression. Our findings demonstrate that ASCL1 is a key chromatin remodeler in human neurogenesis, uncovering an alternative mechanism of remodeling function dependent on partner ATPase activity.

U2 - 10.1101/2022.10.09.510609

DO - 10.1101/2022.10.09.510609

M3 - Preprint

BT - ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation

PB - bioRxiv

ER -

ASCL1 interacts with the mSWI/SNF at distal regulatory elements to regulate neural differentiation

Abstract

Access to Document

Fingerprint

Cite this