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Dynamic hydroxymethylation of DNA marks differentiation-driven enhancers

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

ORGANISM(S): Mus musculus

PROVIDER: GSE27436 | GEO | 2012/06/04

SECONDARY ACCESSION(S): PRJNA137083

REPOSITORIES: GEO

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Dynamic hydroxymethylation of DNA marks differentiation-driven enhancers

Project description:This SuperSeries is composed of the following subset Series: GSE27334: Whole-genome gene expression level changes in P19.6 mouse embryonal carcinoma cells compared to P19.6 cells treated for 48 hours with all-trans retinoic acid GSE33067: Whole-genome mapping of MEIS1, TET1, H3K4me2 and H3K27ac in P19.6 mouse embryonal carcinoma cells and P19.6 cells treated for 48 hours with all-trans retinoic acid GSE38407: Genome-wide mapping of 5-hydroxymethylcytosine (5hmC) during differentiation of P19.6 and 3T3-L1 cells Refer to individual Series

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Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.

Project description:Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.

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

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