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Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ATAC-Seq]

ABSTRACT: Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ATAC-Seq]

PROVIDER: PRJNA1230563 | ENA |

REPOSITORIES: ENA

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Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ChIP-Seq]

Project description:Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ChIP-Seq]

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Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ChIP-Seq]

Project description:Transcription factors (TFs) recognize specific target sites within cis-regulatory regions to control gene expression. Prokaryotic TFs combine 1D and 3D diffusion mechanisms to efficiently locate their binding sites. In contrast, the determinants of target search efficiency of eukaryotic TFs within the chromatinized genome are poorly characterized. Here we combine in vivo and in vitro single molecule imaging to dissect the role of charged disordered regions of the mammalian Sox2 and Sox17 TFs in their ability to search for their binding sites. We demonstrate that the DBD flanking region of Sox2 (DFRSox2) dramatically enhances Sox2 search efficiency as compared to the negatively-charged DFRSox17 through distinct mechanisms on naked versus nucleosomal DNA. Enhanced search on naked DNA is primarily mediated by an increase in target recognition rate during 1D sliding. In contrast, target site recognition within nucleosomal DNA is mainly enhanced by increased nonspecific interactions with nucleosomes, facilitating binding to closed chromatin and reinforcing pioneering activity. These findings provide critical insights into the biophysical mechanisms governing TF target search beyond the DBD, and demonstrate how charged disordered regions modulate TF target search on the chromatinized genome.

2025-04-02 | GSE290874 | GEO

Electrostatic properties of disordered regions control transcription factor search and pioneer activity [ATAC-Seq]

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Defining the mechanisms and properties of post-transcriptional regulatory disordered regions by high-throughput functional profiling

Project description:Disordered regions within RNA binding proteins are required to control mRNA decay and protein synthesis. To understand how these disordered regions modulate gene expression, we surveyed regulatory activity across the entire disordered proteome using a high-throughput functional assay. We identified hundreds of regulatory sequences within intrinsically disordered regions and demonstrate how these elements cooperate with core mRNA decay machinery to promote transcript turnover. Coupling high-throughput functional profiling with mutational scanning revealed diverse molecular features, ranging from defined motifs to overall sequence composition, underlying the regulatory effects of disordered peptides. Machine learning analysis implicated aromatic residues in particular contexts as critical determinants of repressor activity, consistent with their roles in forming protein-protein interactions with downstream effectors. Our results define the molecular principles and biochemical mechanisms that govern post-transcriptional gene regulation by disordered regions and exemplify the encoding of diverse yet specific functions in the absence of well-defined structure.

2024-02-02 | GSE254492 | GEO

Defining the mechanisms and properties of post-transcriptional regulatory disordered regions by high-throughput functional profiling

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Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells

Project description:Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells

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Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [RNA-seq]

Project description:Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [RNA-seq]

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Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [ATAC-seq]

Project description:Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [ATAC-seq]

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Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [ChIP-seq]

Project description:Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells [ChIP-seq]

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Mitotic chromosome binding predicts transcription factor properties in interphase [ChIP-Seq]

Project description:Mammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/ non-specific DNA binding affinity. How these properties affect the ability of TFs to occupy their specific binding sites in the genome and modify the epigenetic landscape is unclear. Here we combined live cell quantitative measurements of mitotic chromosome binding (MCB) of 502 TFs, measurements of TF mobility by fluorescence recovery after photobleaching, single molecule imaging of DNA binding in live cells, and genome-wide mapping of TF binding and chromatin accessibility. MCB scaled with interphase properties such as association with DNA-rich compartments, mobility, as well as large differences in genome-wide specific site occupancy that correlated with TF impact on chromatin accessibility. As MCB is largely mediated by electrostatic, non-specific TF-DNA interactions, our data suggests that non-specific DNA binding of TFs enhances their search for specific sites and thereby their impact on the accessible chromatin landscape.

2019-01-25 | GSE119782 | GEO

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