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Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Mnase-seq]

ABSTRACT: Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Mnase-seq]

PROVIDER: PRJNA910209 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22580067_1.fastq.gz	Fastqsanger.gz
	SRR22580067_2.fastq.gz	Fastqsanger.gz
	SRR22580068_1.fastq.gz	Fastqsanger.gz
	SRR22580068_2.fastq.gz	Fastqsanger.gz

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Different chromatin scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2

Project description:Different chromatin scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2

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Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Mnase-seq]

Project description:Pioneer transcription factors, by interacting with nucleosomes, scan silent, compact chromatin to target regulatory sequences, enabling cooperative binding events that modulate local chromatin structure and gene activity. However, not all cognate motifs are targeted by pioneer factors and dynamic scanning parameters required to scan compact chromatin are unknown. A combined genomics and single-molecule tracking approach shows that to target DNase-resistant, low-histone turnover sites, pioneer factors FOXA1 and SOX2 display opposite dynamics of chromatin scanning: slow, with low nucleoplasmic diffusion and stable interactions, versus fast, with high nucleoplasmic diffusion and transient interactions, respectively. Despite such differences, the ability of FOXA1 and SOX2 to scan low-mobility chromatin, mediated by protein domains outside of the respective DNA binding domains, leads to targeting silent chromatin. By contrast, non-pioneer HNF4A predominantly targets DNase-sensitive, nucleosome-depleted regions. We conclude that the targeting of compact chromatin sites by pioneer factors can be performed through diverse dynamic processes. Micrococcol nuclease digestion and sequencing (MNase-seq) of human BJ fibroblasts

2023-06-07 | GSE220569 | GEO

Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Cut&Run]

Project description:Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Cut&Run]

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Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [ChIP-seq]

Project description:Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [ChIP-seq]

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Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [Cut&Run]

Project description:Pioneer transcription factors, by interacting with nucleosomes, scan silent, compact chromatin to target regulatory sequences, enabling cooperative binding events that modulate local chromatin structure and gene activity. However, not all cognate motifs are targeted by pioneer factors and dynamic scanning parameters required to scan compact chromatin are unknown. A combined genomics and single-molecule tracking approach shows that to target DNase-resistant, low-histone turnover sites, pioneer factors FOXA1 and SOX2 display opposite dynamics of chromatin scanning: slow, with low nucleoplasmic diffusion and stable interactions, versus fast, with high nucleoplasmic diffusion and transient interactions, respectively. Despite such differences, the ability of FOXA1 and SOX2 to scan low-mobility chromatin, mediated by protein domains outside of the respective DNA binding domains, leads to targeting silent chromatin. By contrast, non-pioneer HNF4A predominantly targets DNase-sensitive, nucleosome-depleted regions. We conclude that the targeting of compact chromatin sites by pioneer factors can be performed through diverse dynamic processes. Cleavage under Targets and Release Using Nuclease (CUT&RUN) of SOX2 and SOX2-DBD after ectopic expression in BJ fibroblasts.

2023-06-07 | GSE220568 | GEO

Distinct Chromatin Scanning Modes Lead to Targeting of Compacted Chromatin by Pioneer Factors FOXA1 and SOX2 [ChIP-seq]

Project description:Pioneer transcription factors, by interacting with nucleosomes, scan silent, compact chromatin to target regulatory sequences, enabling cooperative binding events that modulate local chromatin structure and gene activity. However, not all cognate motifs are targeted by pioneer factors and dynamic scanning parameters required to scan compact chromatin are unknown. A combined genomics and single-molecule tracking approach shows that to target DNase-resistant, low-histone turnover sites, pioneer factors FOXA1 and SOX2 display opposite dynamics of chromatin scanning: slow, with low nucleoplasmic diffusion and stable interactions, versus fast, with high nucleoplasmic diffusion and transient interactions, respectively. Despite such differences, the ability of FOXA1 and SOX2 to scan low-mobility chromatin, mediated by protein domains outside of the respective DNA binding domains, leads to targeting silent chromatin. By contrast, non-pioneer HNF4A predominantly targets DNase-sensitive, nucleosome-depleted regions. We conclude that the targeting of compact chromatin sites by pioneer factors can be performed through diverse dynamic processes. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HNF4A, FOXA1, FOXA1-DBD, FOXA1-NHAA, FOXA1-RRAA, as well as H2B-HALO after ectopic expression in human BJ fibroblast cells.

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Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2.

Project description:Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer factors access chromatin by assisted loading with other transcription factors, the nucleosome-binding properties of pioneer factors enable them to initiate zygotic genome activation, embryonic development, and cellular reprogramming. To better understand nucleosome targeting in vivo, we assess whether pioneer factors FoxA1 and Sox2 target stable or unstable nucleosomes and find that they target DNase-resistant, stable nucleosomes, whereas HNF4A, a non-nucleosome binding factor, targets open, DNase-sensitive chromatin. Despite FOXA1 and SOX2 targeting similar proportions of DNase-resistant chromatin, using single-molecule tracking, we find that FOXA1 uses lower nucleoplasmic diffusion and longer residence times while SOX2 uses higher nucleoplasmic diffusion and shorter residence times to scan compact chromatin, while HNF4 scans compact chromatin much less efficiently. Thus, pioneer factors target compact chromatin through distinct processes.

| S-EPMC10529229 | biostudies-literature

Different chromatin scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2

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

2023-06-06 | GSE220570 | 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

Single cell RNA-sequencing of pre-implantation marmoset embryos from the four-cell to compacted morula

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