RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.
RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.
复制标题
DOI：
10.1016/j.molcel.2016.11.030
复制
发表时间：
2017-01-19
期刊：
影响因子：
16
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhang H;Gan H;Wang Z;Lee JH;Zhou H;Ordog T;Wold MS;Ljungman M;Zhang Z
The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions including promoters, enhancers and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through an shRNA screening, we identified single-stranded DNA binding protein RPA as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and co-localizes with HIRA and H3.3 at gene promoters and enhancers. Depletion of RPA1, the largest subunit of the RPA complex, dramatically reduces both HIRA association with chromatin and the deposition of newly synthesized H3.3 at promoters and enhancers and leads to altered transcription at gene promoters. These results support a model whereby RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation. RPA is a DNA binding protein involved in DNA replication and repair. Zhang et al show that RPA is also involved in nucleosome assembly of histone H3 variant H3.3. RPA recruits histone chaperone HIRA, which deposits newly synthesized H3.3 into gene regulatory elements.
