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The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes

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

ORGANISM(S): Drosophila sechellia Drosophila ananassae Drosophila mojavensis Drosophila persimilis Drosophila erecta Drosophila simulans Drosophila willistoni Drosophila yakuba Homo sapiens Drosophila virilis Drosophila melanogaster Drosophila pseudoobscura

PROVIDER: GSE102441 | GEO | 2018/06/04

REPOSITORIES: GEO

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The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes.

Project description:Transcriptional enhancers function as docking platforms for combinations of transcription factors (TFs) to control gene expression. How enhancer sequences determine nucleosome occupancy, TF recruitment and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains, we found that SNPs affecting binding sites of the TF Grainy head (Grh) causally determine the accessibility of epithelial enhancers. We show that deletion and ectopic expression of Grh cause loss and gain of DNA accessibility, respectively. However, although Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs-GRHL1, GRHL2 and GRHL3-function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers but not for their activation. Our data support a model positing that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.

| S-EPMC6031307 | biostudies-literature

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [scATAC-seq]

Project description:Transcriptional enhancers function as docking platforms for combinations of transcription factors to control gene expression. How enhancer sequences determine nucleosome occupancy, transcription factor recruitment, and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains we found that SNPs affecting Grainyhead binding sites causally determine the accessibility of epithelial enhancers. We show that deletion or ectopic expression of Grh causes loss or gain of DNA accessibility, respectively. However, while Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs, GRHL1/2/3, function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers, but not for their activation. Our data support the model that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.

2018-06-04 | GSE102544 | GEO

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [ATAC-seq]

2018-06-04 | GSE101827 | GEO

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [evolutionary study]

2018-06-04 | GSE102439 | GEO

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [ATAC-seq Grh mutants and Human GRHL]

2018-06-04 | GSE108019 | GEO

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes

Project description:The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes

| PRJNA397746 | ENA

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [evolutionary study]

Project description:The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [evolutionary study]

| PRJNA397749 | ENA

The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [ATAC-seq Grh mutants and Human GRHL]

Project description:The transcription factor Grainyhead primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes [ATAC-seq Grh mutants and Human GRHL]

| PRJNA422244 | ENA

Nucleosomes accelerate transcription factor dissociation.

Project description:Transcription factors (TF) bind DNA-target sites within promoters to activate gene expression. TFs target their DNA-recognition sequences with high specificity by binding with resident times of up to hours in vitro. However, in vivo TFs can exchange on the order of seconds. The factors that regulate TF dynamics in vivo and increase dissociation rates by orders of magnitude are not known. We investigated TF binding and dissociation dynamics at their recognition sequence within duplex DNA, single nucleosomes and short nucleosome arrays with single molecule total internal reflection fluorescence (smTIRF) microscopy. We find that the rate of TF dissociation from its site within either nucleosomes or nucleosome arrays is increased by 1000-fold relative to duplex DNA. Our results suggest that TF binding within chromatin could be responsible for the dramatic increase in TF exchange in vivo. Furthermore, these studies demonstrate that nucleosomes regulate DNA-protein interactions not only by preventing DNA-protein binding but by dramatically increasing the dissociation rate of protein complexes from their DNA-binding sites.

| S-EPMC3950707 | biostudies-literature

The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation.

Project description:Enhancers play a central role in precisely regulating the expression of developmentally regulated genes. However, the machineries required for enhancer-promoter communication have remained largely unknown. We have found that Ell3, a member of the Ell (eleven-nineteen lysine-rich leukemia gene) family of RNA Pol II elongation factors, occupies enhancers in embryonic stem cells. Ell3's association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of developmentally regulated genes and for the recruitment of the super elongation complex (SEC) to these loci following differentiation signals. Furthermore, Ell3 binding to inactive or poised enhancers is essential for stem cell specification. We have also detected the presence of Pol II and Ell3 in germ cell nuclei. These findings raise the possibility that transcription factors could prime gene expression by marking enhancers in ES cells or even as early as in the germ cell state.

| S-EPMC3556173 | biostudies-literature

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