Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide identification of Grainy head targets in Drosophila [gene expression]

ABSTRACT: Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions, we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU-domain TF, Vvl, (ventral veins lacking) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE102549 | GEO | 2017/08/12

SECONDARY ACCESSION(S): PRJNA398028

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide identification of Grainy head targets in Drosophila [ChIP-seq]

Project description:Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions, we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU-domain TF, Vvl, (ventral veins lacking) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.

2017-08-12 | GSE102550 | GEO

Stable Binding of the Conserved Transcription Factor Grainy Head to Its Target Genes Throughout Drosophila melanogaster Development

Project description:It has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct binding events allow Grh to control cell fate specification in different tissue types, we used a combination of ChIP-seq and RNA-seq to elucidate the gene regulatory network controlled by Grh during four stages of embryonic development (spanning stages 5-17) and in larval tissue. Contrary to expectations, we discovered that Grh remains bound to at least 1146 genomic loci over days of development. In contrast to this stable DNA occupancy, the subset of genes whose expression is regulated by Grh varies. Grh transitions from functioning primarily as a transcriptional repressor early in development to functioning predominantly as an activator later. Our data reveal that Grh binds to target genes well before the Grh-dependent transcriptional program commences, suggesting it sets the stage for subsequent recruitment of additional factors that execute stage-specific Grh functions.

2017-02-02 | GSE83305 | GEO

Developmentally regulated requirement for the conserved transcription factor Grainy head in determining chromatin accessibility

Project description:Pioneer transcription factors initiate changes in gene expression by binding to cis-regulatory modules and promoting chromatin accessibility. It is suggested that this activity is an essential first step in priming these sites for the binding of other factors. Nonetheless, it is unclear whether pioneering activity is always required when these factors are present during development. The highly conserved, essential transcription factor Grainy head was recently identified as a pioneer factor in Drosophila larval imaginal discs, yet Grainy head is present throughout development. To determine whether Grainy head maintains its pioneering role throughout development, we performed ATAC-seq on embryos lacking either maternal or zygotic Grainy head at three stages of development (stage 5, stage 6, and stage 15). Surprisingly, we discovered that neither maternal nor zygotic Grainy head are required for chromatin accessibility in early embryogenesis. Nonetheless, we find that Grainy head binding is correlated with some cis-regulatory modules that gain chromatin accessibility at gastrulation. Intriguingly, later in embryogenesis Grainy head gains a role in promoting chromatin accessibility. Additionally, we determined that Grainy head is able to remain bound to mitotic chromatin, like other pioneer factors, yet this ability is separate from its pioneering activity. Our data reveal that Grainy head pioneering activity is temporally, suggesting that other unidentified pioneer factors compensate for the loss of Grainy head.

2020-02-26 | GSE137075 | GEO

A combined genomic approach unveils the transcriptional basis of heterogeneity of human pancreatic ductal adenocarcinoma [RNA-seq]

Project description:The histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).

2016-01-18 | E-GEOD-64558 | biostudies-arrayexpress

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 [evolutionary study]

2018-06-04 | GSE102439 | 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 [ATAC-seq Grh mutants and Human GRHL]

2018-06-04 | GSE108019 | GEO

Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer [RNA-seq]

2016-01-18 | GSE64558 | GEO

Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer [ChIP-seq]

2016-01-18 | GSE64557 | GEO