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Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions

ABSTRACT: Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions

PROVIDER: PRJNA686407 | ENA |

REPOSITORIES: ENA

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Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [competition]

Project description:Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [competition]

| PRJNA686408 | ENA

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [titration]

Project description:Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [titration]

| PRJNA686411 | ENA

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [competition]

Project description:Most eukaryotic transcription factors (TFs) are part of large protein families, with members of the same family (i.e. paralogous TFs) recognizing similar DNA-binding motifs but performing different regulatory functions. Many TF paralogs are co-expressed in the cell, and thus can compete for target sites across the genome. Here, we show that direct competition for DNA binding between TF paralogs is a major determinant of their genomic binding patterns. Using yeast proteins Cbf1 and Pho4 as our model system, we designed a high-throughput quantitative assay to capture the genomic binding profiles of competing TFs in a cell-free system. Our data shows that Cbf1 and Pho4 greatly influence each other’s occupancy by competing for their common putative genomic binding sites. The competition is different at different genomic sites, as dictated by the TFs' expression levels and their divergence in DNA-binding specificity and affinity. Analyses of ChIP-seq data show that the biophysical rules that dictate the competitive TF binding patterns in vitro are also followed in vivo, in the complex cellular environment. Furthermore, the Cbf1-Pho4 competition for genomic sites, as characterized in vitro using our new assay, plays a critical role in the specific activation of their target genes in the cell. Overall, our study highlights the importance of direct TF-TF competition for genomic binding and gene regulation by TF paralogs, and proposes an approach for studying this competition in a quantitative and high-throughput manner.

2021-04-22 | GSE163509 | GEO

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions [titration]

2021-04-22 | GSE163511 | GEO

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions.

Project description:Most eukaryotic transcription factors (TFs) are part of large protein families, with members of the same family (i.e., paralogous TFs) recognizing similar DNA-binding motifs but performing different regulatory functions. Many TF paralogs are coexpressed in the cell and thus can compete for target sites across the genome. However, this competition is rarely taken into account when studying the in vivo binding patterns of eukaryotic TFs. Here, we show that direct competition for DNA binding between TF paralogs is a major determinant of their genomic binding patterns. Using yeast proteins Cbf1 and Pho4 as our model system, we designed a high-throughput quantitative assay to capture the genomic binding profiles of competing TFs in a cell-free system. Our data show that Cbf1 and Pho4 greatly influence each other's occupancy by competing for their common putative genomic binding sites. The competition is different at different genomic sites, as dictated by the TFs' expression levels and their divergence in DNA-binding specificity and affinity. Analyses of ChIP-seq data show that the biophysical rules that dictate the competitive TF binding patterns in vitro are also followed in vivo, in the complex cellular environment. Furthermore, the Cbf1-Pho4 competition for genomic sites, as characterized in vitro using our new assay, plays a critical role in the specific activation of their target genes in the cell. Overall, our study highlights the importance of direct TF-TF competition for genomic binding and gene regulation by TF paralogs, and proposes an approach for studying this competition in a quantitative and high-throughput manner.

| S-EPMC8256859 | biostudies-literature

Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions

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

2021-04-22 | GSE163512 | GEO

Competition between DNA methylation and transcription factors determines binding of NRF1

Project description:Competition between DNA methylation and transcription factors determines binding of NRF1

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Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome

Project description:Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome

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Chromatin environment and cellular context specify compensatory activity of paralogous MEF2 transcription factors

Project description:Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes. Despite the prevalence of this phenomenon, an in vivo genome-scale understanding of how TFs dynamically respond to paralog depletion is still needed. We explore this question in the mammalian brain by studying the highly conserved MEF2 family of TFs, which confer phenotypic robustness in multiple brain regions. Employing single and double conditional knockout of MEF2A and MEF2D in granule neurons of the mouse cerebellum, we find MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. To explore the molecular basis underlying this phenomenon, we systematically characterize in vivo genome-wide occupancy of MEF2A and MEF2D in the presence or absence of one another. Although highly co-expressed in granule neurons, MEF2D is the predominant genomic regulator of gene expression. Strikingly, upon depletion of MEF2D, the occupancy of MEF2A robustly increases at a subset of sites normally bound to MEF2D. Epigenome and transcriptome analyses reveal that sites experiencing compensatory MEF2A occupancy undergo functional compensation for genomic activation and gene expression. In contrast, a distinct population of sites without compensatory MEF2A activity undergo significant dysregulation upon loss of MEF2D. The two populations of MEF2 target sites are further stratified by relative chromatin accessibility, with compensatory MEF2A activity concentrated within more open chromatin. Finally, we reveal that motor activity-induced changes in neuronal state induce a dynamic switch from non-compensatory to compensatory MEF2-dependent gene regulation, demonstrating the context-dependent nature of paralogous TF interdependency. Collectively, these studies define the first in vivo genome-wide characterization of functional interdependency between paralogous TFs.

2019-09-26 | GSE138028 | GEO

Competition between PRC2.1 and 2.2 subcomplexes regulates PRC2 chromatin occupancy in human stem cells

Project description:Competition between PRC2.1 and 2.2 subcomplexes regulates PRC2 chromatin occupancy in human stem cells

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