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The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE208072 | GEO | 2023/05/05

REPOSITORIES: GEO

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The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates [RNA-Seq]

Project description:When stem cells activate a member of the SOX family of pioneer factors, they bind their cognate sequences within condensed chromatin, not only evicting the associated nucleosome, but also recruiting H3K4-monomethylases, which modify flanking nucleosomes to open chromatin and activate one lineage program; simultaneously, pioneer factors also silence alternative fates, but in this case act indirectly, through competing for H3K4-monomethylases pre-existing at the original fate genes.

2023-05-05 | GSE208071 | GEO

The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates [CUT&RUN]

2023-05-05 | GSE208070 | GEO

The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates [ATAC-Seq]

2023-05-05 | GSE208066 | GEO

The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates [MINT ChIP-Seq]

2023-05-05 | GSE208069 | GEO

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers.

Project description:Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation.

| S-EPMC3065703 | biostudies-literature

Genetic determinants and epigenetic effects of pioneer-factor occupancy.

Project description:Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.

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Genetic determinants and epigenetic effects of pioneer factor binding

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-01-29 | GSE90456 | GEO

CLK:BMAL1 is a pioneer-like transcription factor

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-06 | E-GEOD-47145 | biostudies-arrayexpress

Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-21 | E-GEOD-47194 | biostudies-arrayexpress

Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.

Project description:Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.

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