Suppression and recovery of BRCA1-mediated transcription by HP1γ via modulation of promoter occupancy.
Suppression and recovery of BRCA1-mediated transcription by HP1γ via modulation of promoter occupancy.
复制标题
DOI：
10.1093/nar/gks947
复制
发表时间：
2012-12
影响因子：
14.9
通讯作者：
Lee JS
中科院分区：
文献类型：
--
作者：
Choi JD;Park MA;Lee JS
异染色质蛋白1γ (HP1γ)是一种参与基因沉默的染色质蛋白。在这里，我们发现HP1γ与乳腺癌1型易感蛋白（BRCA1）相互作用，并通过调节启动子占用和组蛋白修饰来调节BRCA1介导的转录。我们使用了几个HP1γ突变体和组蛋白甲基转移酶的小干扰rna来证明BRCA1-HP1γ相互作用，而不是甲基化组蛋白结合，在HP1γ抑制brca1介导的转录中是重要的。对DNA损伤后启动子关联和组蛋白甲基化的延时研究表明，在DNA损伤前，HP1γ在启动子处积累，而在损伤后，BRCA1在启动子处募集，而驻留在启动子上的HP1γ被拆卸。重要的是，HP1γ组装在损伤释放后以BRCA1-HP1γ相互作用依赖的方式恢复，并靶向SUV39H1。启动子上HP1γ/SUV39H1的修复导致BRCA1解体和组蛋白甲基化，之后转录抑制恢复。我们提出，通过与BRCA1的相互作用，HP1γ在恢复过程中被引导到BRCA1目标启动子，并在DNA损伤时参与BRCA1介导的转录的激活-抑制开关和恢复。
Heterochromatin protein 1γ (HP1γ) is a chromatin protein involved in gene silencing. Herein, we show that HP1γ interacts with breast cancer type 1 susceptibility protein (BRCA1) and regulates BRCA1-mediated transcription via modulation of promoter occupancy and histone modification. We used several HP1γ mutants and small interfering RNAs for histone methyltransferases to show that BRCA1–HP1γ interaction, but not methylated histone binding, is important in HP1γ repression of BRCA1-mediated transcription. Time-lapse studies on promoter association and histone methylation after DNA damage revealed that HP1γ accumulates at the promoter before DNA damage, but BRCA1 is recruited at the promoter after the damage while promoter-resident HP1γ is disassembled. Importantly, HP1γ assembly recovers after release from the damage in a BRCA1–HP1γ interaction-dependent manner and targets SUV39H1. HP1γ/SUV39H1 restoration at the promoter results in BRCA1 disassembly and histone methylation, after which transcription repression resumes. We propose that through interaction with BRCA1, HP1γ is guided to the BRCA1 target promoter during recovery and functions in the activation-repression switch and recovery from BRCA1-mediated transcription in response to DNA damage.
登录
查看更多内容
影响因子：
7.7
作者：
Muchardt, C;Guillemé, M;Yaniv, M
通讯作者：
Yaniv, M
影响因子：
11.4
作者：
Tachibana, Makoto;Matsumura, Yasuko;Shinkai, Yoichi
通讯作者：
Shinkai, Yoichi
影响因子：
64.8
作者：
Lee, JS;Collins, KM;Chung, JH
通讯作者：
Chung, JH
影响因子：
11.4
作者：
Meehan, RR;Kao, CF;Pennings, S
通讯作者：
Pennings, S
HP1 蛋白家族：掌控染色质
影响因子：
4
作者：
Eissenberg, JC;Elgin, SCR
通讯作者：
Elgin, SCR