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MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers

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

ORGANISM(S): Mus musculus

PROVIDER: GSE61392 | GEO | 2015/03/19

SECONDARY ACCESSION(S): PRJNA260925

REPOSITORIES: GEO

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MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers.

Project description: Not available

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MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers (ChIP-Seq)

Project description:Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites, and redirects it to retina-specific enhancers that lack the consensus MEF2 sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs, and through cooperative activation of these enhancers to regulate tissue-specific genes.

2015-03-19 | GSE61391 | GEO

MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers (RNA-Seq)

2015-03-19 | GSE61389 | GEO

MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers

Project description:MEF2D drives photoreceptor development through a genome-wide competition for tissue-specific enhancers

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Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities

Project description:Macrophages reside in essentially all tissues of the body and play key roles in innate and adaptive immune responses. Distinct populations of tissue macrophages also acquire context-specific functions that are important for normal tissue homeostasis. To investigate mechanisms responsible for tissue-specific functions, we analyzed the transcriptomes and enhancer landscapes of brain microglia and resident macrophages of the peritoneal cavity. In addition, we exploited natural genetic variation as a genome-wide “mutagenesis” strategy to identify DNA recognition motifs for transcription factors that promote common or subset-specific binding of the macrophage lineage-determining factor PU.1. We find that distinct tissue environments drive divergent programs of gene expression by differentially activating a common enhancer repertoire and by inducing the expression of divergent secondary transcription factors that collaborate with PU.1 to establish tissue-specific enhancers. These findings provide insights into molecular mechanisms by which tissue environment influences macrophage phenotypes that are likely to be broadly applicable to other cell types. Chromatin marks H3K4me2, H3K27Ac, and transcription factors PU.1 were assessed by ChIP-Seq and RNA-Seq were used to measure gene expression in 5 different macrophage subtypes.

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