RRC ID 50019
著者 Suzuki T, Shimizu Y, Furuhata E, Maeda S, Kishima M, Nishimura H, Enomoto S, Hayashizaki Y, Suzuki H.
タイトル RUNX1 regulates site specificity of DNA demethylation by recruitment of DNA demethylation machineries in hematopoietic cells.
ジャーナル Blood Adv
Abstract RUNX1 is an essential master transcription factor in hematopoietic development and plays important roles in immune functions. Although the gene regulatory mechanism of RUNX1 has been characterized extensively, the epigenetic role of RUNX1 remains unclear. Here, we demonstrate that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. Overexpression analysis of RUNX1 showed the RUNX1-binding site-directed DNA demethylation. The RUNX1-mediated DNA demethylation was also observed in DNA replication-arrested cells, suggesting an involvement of active demethylation mechanism. Coimmunoprecipitation in hematopoietic cells showed physical interactions between RUNX1 and DNA demethylation machinery enzymes TET2, TET3, TDG, and GADD45. Further chromatin immunoprecipitation sequencing revealed colocalization of RUNX1 and TET2 in the same genomic regions, indicating recruitment of DNA demethylation machinery by RUNX1. Finally, methylome analysis revealed significant overrepresentation of RUNX1-binding sites at demethylated regions during hematopoietic development. Collectively, the present data provide evidence that RUNX1 contributes site specificity of DNA demethylation by recruitment of TET and other demethylation-related enzymes to its binding sites in hematopoietic cells.
巻・号 1(20)
ページ 1699-1711
公開日 2017-9-12
DOI 10.1182/bloodadvances.2017005710
PII 2017/005710
PMID 29296817
PMC PMC5728331
IF 4.91
引用数 17
リソース情報
遺伝子材料 CSII-EF-RfA (RDB04387)
ヒト・動物細胞 253G1(HPS0002)