Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [MNase-seq]

ABSTRACT: Control over the accessibility of the genomic cis-regulatory information is key for the accurate deployment of gene expression programs. Such control is exerted by the combined action of pioneer transcription factors and chromatin remodelers with different ability to alter nucleosome positioning and occupancy. Here we show that SMARCA5 ( SNF2H), a chromatin remodeler enforcing linker DNA length, controls spacing of nucleosomes adjacent to sites where the myeloid lineage determining and pioneer TF PU.1 is constitutively bound, without however affecting PU.1 binding. Loss of SMARCA5 caused a widespread increase in the accessibility of sites for stimulus-regulated TFs, causing not only macrophage hyper-activation in response to inflammatory stimulation but also the induction of stimulus-inappropriate genes. SMARCA5 deficiency also determined the extensive increase in binding of C/EBPb to cognate sites normally not accessible in macrophages but instead exposed in white or brown adipogenesis. Overall, enforcement of nucleosome phasing by ISWI controls fidelity in both lineage specification and response to stimulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE284513 | GEO | 2025/09/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [RNA-Seq]

Project description:Control over the accessibility of the genomic cis-regulatory information is key for the accurate deployment of gene expression programs. Such control is exerted by the combined action of pioneer transcription factors and chromatin remodelers with different ability to alter nucleosome positioning and occupancy. Here we show that SMARCA5 ( SNF2H), a chromatin remodeler enforcing linker DNA length, controls spacing of nucleosomes adjacent to sites where the myeloid lineage determining and pioneer TF PU.1 is constitutively bound, without however affecting PU.1 binding. Loss of SMARCA5 caused a widespread increase in the accessibility of sites for stimulus-regulated TFs, causing not only macrophage hyper-activation in response to inflammatory stimulation but also the induction of stimulus-inappropriate genes. SMARCA5 deficiency also determined the extensive increase in binding of C/EBPb to cognate sites normally not accessible in macrophages but instead exposed in white or brown adipogenesis. Overall, enforcement of nucleosome phasing by ISWI controls fidelity in both lineage specification and response to stimulation.

2025-09-18 | GSE289677 | GEO

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [ChIP-seq]

2025-09-18 | GSE289675 | GEO

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [ATAC-seq]

2025-09-18 | GSE289674 | GEO

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [scRNA-seq]

2025-09-18 | GSE297296 | GEO

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [ChIP-seq 2]

2025-09-18 | GSE297981 | GEO

Fidelity in lineage determination and stimulus-inducible gene expression requires ISWI chromatin remodeling activity [RNA-Seq 2]

2025-09-18 | GSE297169 | GEO

A pioneer factor locally opens compacted chromatin to enable targeted ATP-dependent nucleosome remodeling

Project description:Summary: Pioneer transcription factors engage nucleosomal DNA in chromatin to initiate gene regulatory events that control cell fate 1 . To determine how different pioneer transcription factors initiate the formation of a locally accessible environment within silent, compacted chromatin and collaborate with an ATP-dependent chromatin remodeler, we generated nucleosome arrays in vitro with a central nucleosome that can be targeted by the hematopoietic ETS factor PU.1 and bZIP factors C/EBPα, and C/EBPβ. Each class of factor can expose target nucleosomes on linker histone-compacted arrays, but with different hypersensitivity patterns, as discerned by long-read sequencing. The DNA binding domain of PU.1 is sufficient for mononucleosome binding but requires an additional intrinsically disordered domain to bind and open compacted chromatin. The canonical mammalian SWI/SNF (BAF) complex, cBAF, was unable to act upon two forms of locally open chromatin, in the presence of linker histone, unless cBAF was enabled by the acidic- and glutamine-enriched transactivation domain of PU.1. However, cBAF complexes potentiate the nucleosome binding DBD of PU.1 to weakly open chromatin in the absence of the PU.1 unstructured domain. Together our findings provide a mechanism for how pioneer factors initially target chromatin structures to provide specificity for action by nucleosome remodelers that further open local domains.

2022-11-03 | GSE216065 | GEO

HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells

Project description:We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process. We identified several thousand specific regulatory elements (~10% of total DHS sites) that become significantly more or less accessible with sodium butyrate or suberanilohydroxamic acid (SAHA) 72-hour treatments. Most of the differential DNase-hypersensitive (DHS) sites display hallmarks of enhancers; including being enriched for non-promoter regions, associated with nearby gene expression changes, and capable of increasing luciferase reporter expression in K562 cells. Differential DHS sites were enriched for key hematopoietic lineage transcription factor motifs, including SPI1 (PU.1), a known pioneer factor. We found PU.1 becomes up-regulated and increases binding at opened DHS sites by ChIP-seq with HDACi treatment, but show that increased PU.1 protein levels alone are sufficient for only modest increases in chromatin accessibility. PU.1 knockdown by shRNA failed to block the HDACi-induced chromatin accessibility and expression changes in K562, suggesting factors other than PU.1 are responsible for establishment of active enhancers in the HDACi induced differentiation process.

2016-04-10 | GSE74999 | GEO

Dissection of nucleosome remodeling at cis-regulatory elements in stimulated macrophages [chromatin-associated RNA-Seq]

Project description:Dynamic control of the accessibility of the genomic regulatory information is at the heart of stimulus-induced gene expression changes. Whereas chromatin accessibility assays describe dynamic changes in open chromatin over time, they provide only indirect and limited information on the nucleosome remodeling events that underlie such changes. Here, we combined accessibility assays and ChIP-seq on nucleosomes generated by micrococcal nuclease digestion in resting and LPS-activated macrophages. We devised a novel quantitative framework to discriminate different types of nucleosome remodeling events and used it to analyze nucleosome organization at genomic cis-regulatory elements modulated by stimulation on a genomic scale. At typical stimulus-activated enhancers, remodeling events were commonly asymmetric, with only one of the two nucleosomes flanking the central accessible region being remodeled. A systematic analysis of nucleosome organization revealed distinct associations of individual TFs with remodeling and showed that most remodeling events tended to occur early in the response and to be maintained over time, with progressively fewer novel events occurring at later times.

2019-08-01 | GSE119692 | GEO

Dissection of nucleosome remodeling at cis-regulatory elements in stimulated macrophages [ChIP-Seq]

2019-08-01 | GSE119691 | GEO