Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering
Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering
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FOXA1 对 DNA 修复因子的成核将 DNA 去甲基化与转录先驱联系起来
DOI：
10.1038/ng.3635
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发表时间：
2016-08
期刊：
影响因子：
30.8
通讯作者：
Shang Yongfeng
中科院分区：
文献类型：
--
作者：
Zhang Yu;Zhang Di;Li Qian;Liang Jing;Sun Luyang;Yi Xia;Chen Zhe;Yan Ruorong;Xie Guojia;Li Wanjin;Liu Shumeng;Xu Bosen;Li Lei;Yang Jianguo;He Lin;Shang Yongfeng
FOXA 1在表观遗传重编程中起作用，被描述为“先锋因子”。然而，FOXA 1究竟是如何实现这些显著的生物学功能的还没有完全弄清楚。在这里，我们报告FOXA 1与DNA修复复合物相关，并且是人类细胞中DNA聚合酶β（POLB）基因组靶向所必需的。全基因组DNA甲基化组表明FOXA 1 DNA修复复合物以谱系特异性方式与DNA去甲基化功能相关。FOXA 1的消耗导致在大部分FOXA 1结合区域中局部重建甲基化，并且具有最一致的超甲基化的区域表现出最大的POLB损失，并且由活性启动子和增强子代表。因此，FOXA 1的过表达以POLB依赖的方式使其结合位点主动去甲基化。最后，FOXA 1相关的DNA去甲基化与雌激素受体基因组靶向和雌激素反应性紧密相关。总之，这些结果将FOXA 1相关的DNA去甲基化与FOXA 1的转录先驱联系起来。
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.
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影响因子：
10.5
作者：
Menet JS;Pescatore S;Rosbash M
通讯作者：
Rosbash M
影响因子：
64.5
作者：
Rai K;Huggins IJ;James SR;Karpf AR;Jones DA;Cairns BR
通讯作者：
Cairns BR
影响因子：
11.4
作者：
Kubota, Y;Nash, RA;Lindahl, T
通讯作者：
Lindahl, T
影响因子：
64.5
作者：
Malovannaya A;Lanz RB;Jung SY;Bulynko Y;Le NT;Chan DW;Ding C;Shi Y;Yucer N;Krenciute G;Kim BJ;Li C;Chen R;Li W;Wang Y;O'Malley BW;Qin J
通讯作者：
Qin J
DOI：
--
发表时间：
1969-11
期刊：
Zeitschrift fur Krankenpflege. Revue suisse des infirmieres
影响因子：
--
作者：
C. Lanz
通讯作者：
C. Lanz