Unknown,Transcriptomics,Genomics,Proteomics

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Foxd3 binding at enhancers controls developmental timing of gene expression by regulation of histone acetylation [expression array]

ABSTRACT: Transcription factor/enhancer interactions determine cell specific gene expression. Here, we followed enhancers during differentiations of embryonic stem (ESCs) to epiblast like cells (EpiLCs). There were highly dynamic changes in histone lysine 27 acetylation at enhancer sites throughout the genome. These sites were enriched for a Foxd3 binding motif, a forkhead transcription factor essential in early embryonic development. Surprisingly, Foxd3 occupied largely mutually exclusive sites in the ESCs versus EpiLCs. Foxd3 bound to nucleosome occupied regions, simultaneously evicting the histones while inhibiting full gene expression through the recruitment of histone deacetylases. Knockout of Foxd3 resulted in hyperacetylation and transcriptional upregulation of neighboring genes, many of which were further upregulated at later stages of differentiation. These data show that Foxd3 primes enhancer sites during pregastrulation by removing nucleosomes, yet suppresses neighboring histone hyperacetylation. Such a mechanism may be common to many transcription factors that prepare enhancers for later gene activation during development. Total RNA obtained Foxd3 knockout embryonic stem cells (ESCs) and epiblast-like cells (EpiLCs) (treated with 1uM tamoxifen for 36h to induce knockout) compared to wild-type controls

ORGANISM(S): Mus musculus

SUBMITTER: Raga Krishnakumar

PROVIDER: E-GEOD-58317 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Foxd3 binding at enhancers controls developmental timing of gene expression by regulation of histone acetylation [expression array]

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