| Literature DB >> 27500525 |
Yu Zhang1, Di Zhang1, Qian Li1, Jing Liang1, Luyang Sun1, Xia Yi1, Zhe Chen1, Ruorong Yan1, Guojia Xie1, Wanjin Li1, Shumeng Liu1, Bosen Xu1, Lei Li1, Jianguo Yang1, Lin He1, Yongfeng Shang1,2.
Abstract
FOXA1 functions in epigenetic reprogramming and is described as a 'pioneer factor'. However, exactly how FOXA1 achieves these remarkable biological functions is not fully understood. Here we report that FOXA1 associates with DNA repair complexes and is required for genomic targeting of DNA polymerase β (POLB) in human cells. Genome-wide DNA methylomes demonstrate that the FOXA1 DNA repair complex is functionally linked to DNA demethylation in a lineage-specific fashion. Depletion of FOXA1 results in localized reestablishment of methylation in a large portion of FOXA1-bound regions, and the regions with the most consistent hypermethylation exhibit the greatest loss of POLB and are represented by active promoters and enhancers. Consistently, overexpression of FOXA1 commits its binding sites to active DNA demethylation in a POLB-dependent manner. Finally, FOXA1-associated DNA demethylation is tightly coupled with estrogen receptor genomic targeting and estrogen responsiveness. Together, these results link FOXA1-associated DNA demethylation to transcriptional pioneering by FOXA1.Entities:
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Year: 2016 PMID： 27500525 DOI： 10.1038/ng.3635
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330