Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Extensive Chromatin Remodeling and Establishment of Transcription Factor 'Hotspots' during Early Adipogenesis

ABSTRACT: Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPbeta and -delta) to transcription factor 'hotspots'. Our results demonstrate that C/EBPbeta marks a large number of these transcription factor 'hotspots' prior to induction of differentiation and chromatin remodeling and is required for their establishment. Furthermore, a subset of early remodeled C/EBP binding sites persists throughout differentiation and is later occupied by PPAR gamma , indicating that early C/EBP family members, in addition to their well established role in activation of PPAR gamma transcription, may act as pioneering factors for PPAR gamma binding. DNase I hypersensitive chromatin regions and transcription factor binding sites were identified at various time points of 3T3-L1 differentiation using DHS-seq and ChIP-seq, respectively.

ORGANISM(S): Mus musculus

SUBMITTER: Susanne Mandrup

PROVIDER: E-GEOD-27826 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis.

Siersbæk Rasmus R Nielsen Ronni R John Sam S Sung Myong-Hee MH Baek Songjoon S Loft Anne A Hager Gordon L GL Mandrup Susanne S

The EMBO journal 20110322 8

Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynami ...[more]

PMID: 21427703

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Project description:Enhancers are developmentally-controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. Here, we show by genome-wide mapping that the newly discovered DNA modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells as well as 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 like Meis1 in P19 cells and PPARgamma in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5mC 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 Genome-wide 5hmC distribution was determined using hMeDIP-seq. Cells used in this study are P19.6 mouse embryonal carnicoma cells and P19.6 cells treated for 48 hours with 1M-BM-5M all-trans retinoic acid (RA), as well as 3T3-L1 cells and 3T3-L1 derived adipocytes differentiated with dexamethasone, insulin and IBMX (differentiation cocktail - DC). Individual hMeDIP samples from P19.6 ord 3T3-L1 cells were pooled for library preparation. Libraries were prepared and sequenced at the IBL sequencing facility (Lille, France) with an Illumina Genome Analyser II.

Dataset Information

Extensive Chromatin Remodeling and Establishment of Transcription Factor 'Hotspots' during Early Adipogenesis

Publications

Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis.

Similar Datasets

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