Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163 Illkirch Cedex, 67404, C.U. Strasbourg, France.
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
Nat Commun. 2018 Jul 4;9(1):2610. doi: 10.1038/s41467-018-05010-0.
The DNA damage sensor XPC is involved in nucleotide excision repair. Here we show that in the absence of damage, XPC co-localizes with RNA polymerase II (Pol II) and active post-translational histone modifications marks on a subset of class II promoters in human fibroblasts. XPC depletion triggers specific gene down-expression due to a drop in the deposition of histone H3K9 acetylation mark and pre-initiation complex formation. XPC interacts with the histone acetyltransferase KAT2A and specifically triggers the recruitment of the KAT2A-containing ATAC complex to the promoters of down-expressed genes. We show that a strong E2F1 signature characterizes the XPC/KAT2A-bound promoters and that XPC interacts with E2F1 and promotes its binding to its DNA element. Our data reveal that the DNA repair factor XPC is also an RNA polymerase II cofactor recruiting the ATAC coactivator complex to promoters by interacting with the DNA binding transcription factor E2F1.
DNA 损伤传感器 XPC 参与核苷酸切除修复。在这里，我们表明，在没有损伤的情况下，XPC 与人成纤维细胞中 II 类启动子的一部分与 RNA 聚合酶 II（Pol II）和活跃的翻译后组蛋白修饰标记共定位。XPC 耗竭会因组蛋白 H3K9 乙酰化标记和起始前复合物形成的减少而导致特定基因的下调表达。XPC 与组蛋白乙酰转移酶 KAT2A 相互作用，并特异性触发包含 KAT2A 的 ATAC 复合物募集到下调表达基因的启动子。我们表明，强烈的 E2F1 特征表征了 XPC/KAT2A 结合的启动子，并且 XPC 与 E2F1 相互作用并促进其与 DNA 元件结合。我们的数据表明，DNA 修复因子 XPC 也是 RNA 聚合酶 II 的共因子，通过与 DNA 结合转录因子 E2F1 相互作用，将 ATAC 共激活因子复合物募集到启动子。
