GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation
GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation
复制标题
GATA3 与 PARP1 配合通过调节组蛋白 H1 掺入来调节 CCND1 转录
DOI：
10.1038/onc.2013.270
复制
发表时间：
2014-06-12
期刊：
影响因子：
8
通讯作者：
Shi, L.
中科院分区：
文献类型：
--
作者：
Shan, L.;Li, X.;Shi, L.
转录因子 GATA3 是乳腺发育的关键调节因子，也是管腔乳腺癌的明确标志物。然而，GATA3 在乳腺癌发生中的分子机制仍不完全清楚。我们在此报告，GATA3 通过对乳腺癌细胞中 CCND1 基因的转录调节促进 G 1/S 转变，从而促进细胞增殖和肿瘤发生。我们发现 GATA3 在物理上与聚 ADP 核糖聚合酶 1 (PARP1) 相关，PARP1 是一种通过聚 (ADP-核糖基) 化修饰核蛋白的酶。我们发现 PARP1 在乳腺癌细胞中充当 GATA3 的转录共激活子，并证明 GATA3 与 PARP1 合作参与 CCND1 基因的反式激活。我们证明 PARP1 与接头组蛋白 H1 竞争以维持 CCND1 基因的转录活性染色质环境。我们的结果揭示了 GATA3 和 PARP1 在转录激活中协调调节的分子基础，为 GATA3 在乳腺癌发生中提供了机制。
The transcription factor GATA3 is a key regulator of mammary gland development and a definitive marker of luminal breast cancer. However, the molecular mechanisms underlying the role of GATA3 in breast carcinogenesis is still not fully understood. We report here that GATA3 promotes cell proliferation and tumorigenesis by facilitating the G 1/S transition through its transcription regulation of the CCND1 gene in breast cancer cells. We found that GATA3 is physically associated with poly-ADP ribose polymerase-1 (PARP1), an enzyme modifying nuclear proteins by poly (ADP-ribosyl) ation. We showed that PARP1 acts as a transcription coactivator for GATA3 in breast cancer cells and demonstrated that GATA3 cooperates with PARP1 in transactivation of the CCND1 gene. We demonstrated that PARP1 competes with linker histone H1 to maintain a transcriptional competent chromatin environment for CCND1 gene. Our results unveiled a molecular basis for the coordinated regulation between GATA3 and PARP1 in transcription activation, providing a mechanism for GATA3 in breast carcinogenesis.