Dataset Information

AP-2? regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.

ABSTRACT: Oestrogen receptor ? (ER?) is key player in the progression of breast cancer. Recently, the cistrome and interactome of ER? were mapped in breast cancer cells, revealing the importance of spatial organization in oestrogen-mediated transcription. However, the underlying mechanism of this process is unclear. Here, we show that ER? binding sites (ERBS) identified from the Chromatin Interaction Analysis-Paired End DiTag of ER? are enriched for AP-2 motifs. We demonstrate the transcription factor, AP-2?, which has been implicated in breast cancer oncogenesis, binds to ERBS in a ligand-independent manner. Furthermore, perturbation of AP-2? expression impaired ER? DNA binding, long-range chromatin interactions, and gene transcription. In genome-wide analyses, we show that a large number of AP-2? and ER? binding events converge together across the genome. The majority of these shared regions are also occupied by the pioneer factor, FoxA1. Molecular studies indicate there is functional interplay between AP-2? and FoxA1. Finally, we show that most ERBS associated with long-range chromatin interactions are colocalized with AP-2? and FoxA1. Together, our results suggest AP-2? is a novel collaborative factor in ER?-mediated transcription.

SUBMITTER: Tan SK

PROVIDER: S-EPMC3155293 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.

Tan Si Kee SK Lin Zhen Hua ZH Chang Cheng Wei CW Varang Vipin V Chng Kern Rei KR Pan You Fu YF Yong Eu Leong EL Sung Wing Kin WK Cheung Edwin E

The EMBO journal 20110513 13

Oestrogen receptor α (ERα) is key player in the progression of breast cancer. Recently, the cistrome and interactome of ERα were mapped in breast cancer cells, revealing the importance of spatial organization in oestrogen-mediated transcription. However, the underlying mechanism of this process is unclear. Here, we show that ERα binding sites (ERBS) identified from the Chromatin Interaction Analysis-Paired End DiTag of ERα are enriched for AP-2 motifs. We demonstrate the transcription factor, AP ...[more]

PMID: 21572391

Similar Datasets

Project description:BackgroundDNA methylation is one way to encode epigenetic information and plays a crucial role in regulating gene expression during embryonic development. DNA methylation marks are established by the DNA methyltransferases and, recently, a mechanism for active DNA demethylation has emerged involving the ten-eleven translocator proteins and thymine DNA glycosylase (TDG). However, so far it is not clear how these enzymes are recruited to, and regulate DNA methylation at, specific genomic loci. A number of studies imply that sequence-specific transcription factors are involved in targeting DNA methylation and demethylation processes. Oestrogen receptor beta (ERβ) is a ligand-inducible transcription factor regulating gene expression in response to the female sex hormone oestrogen. Previously, we found that ERβ deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERβ in DNA methylation. In this study, we set out to explore this involvement on a genome-wide level, and to investigate the underlying mechanisms of this function.ResultsUsing reduced representation bisulfite sequencing, we compared genome-wide DNA methylation in mouse embryonic fibroblasts derived from wildtype and ERβ knock-out mice, and identified around 8000 differentially methylated positions (DMPs). Validation and further characterisation of selected DMPs showed that differences in methylation correlated with changes in expression of the nearest gene. Additionally, re-introduction of ERβ into the knock-out cells could reverse hypermethylation and reactivate expression of some of the genes. We also show that ERβ is recruited to regions around hypermethylated DMPs. Finally, we demonstrate here that ERβ interacts with TDG and that TDG binds ERβ-dependently to hypermethylated DMPs.ConclusionWe provide evidence that ERβ plays a role in regulating DNA methylation at specific genomic loci, likely as the result of its interaction with TDG at these regions. Our findings imply a novel function of ERβ, beyond direct transcriptional control, in regulating DNA methylation at target genes. Further, they shed light on the question how DNA methylation is regulated at specific genomic loci by supporting a concept in which sequence-specific transcription factors can target factors that regulate DNA methylation patterns.

Dataset Information

AP-2? regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.

Publications

AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets