Transcriptional regulation of BRCA1 expression by a metabolic switch.
Transcriptional regulation of BRCA1 expression by a metabolic switch.
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DOI：
10.1038/nsmb.1941
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发表时间：
2010-12
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
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虽然BRCA 1的生殖系突变和遗传性乳腺癌之间的联系是众所周知的，最近的证据表明，改变BRCA 1转录也可能有助于散发形式的乳腺癌。在这里，我们表明，BRCA 1的表达是由一个动态的平衡之间的转录共激活子和共抑制剂，管理组蛋白乙酰化和DNA的可及性BRCA 1启动子。转录辅阻遏物和代谢传感器的驱逐，C-末端结合蛋白（CtBP）在这种调节中起着核心作用。通过雌激素诱导、RNAi耗竭或增加的NAD+/NADH比率从BRCA 1启动子丢失CtBP导致HDAC 1消除、组蛋白乙酰化升高和BRCA 1转录增加。这种“代谢开关”对BRCA 1启动子的染色质标记、DNA可及性和基因表达的主动控制提供了乳腺细胞中热量摄入和肿瘤抑制基因表达之间的重要分子联系。
Though the linkages between germline mutations of BRCA1 and hereditary breast cancer are well known, recent evidence suggests that altered BRCA1 transcription may also contribute to sporadic forms of breast cancer. Here we show that BRCA1 expression is controlled by a dynamic equilibrium between transcriptional co-activators and co-repressors that govern histone acetylation and DNA accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor and metabolic sensor, C-terminal-binding protein (CtBP) plays a central role in this regulation. Loss of CtBP from the BRCA1 promoter through either estrogen induction, RNAi depletion or increased NAD+/NADH ratio results in HDAC1 dismissal, elevated histone acetylation, and increased BRCA1 transcription. The active control of chromatin marks, DNA accessibility and gene expression at the BRCA1 promoter by this “metabolic switch” provides an important molecular link between caloric intake and tumor suppressor expression in mammary cells.
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影响因子：
11.2
作者：
De Siervi A;De Luca P;Byun JS;Di LJ;Fufa T;Haggerty CM;Vazquez E;Moiola C;Longo DL;Gardner K
通讯作者：
Gardner K
影响因子：
8
作者：
Blackshear, PE;Goldsworthy, SM;Davis, BJ
通讯作者：
Davis, BJ
DOI：
10.1073/pnas.95.18.10493
发表时间：
1998-09-01
影响因子：
11.1
作者：
Ferreira, R;Magnaghi-Jaulin, L;Trouche, D
通讯作者：
Trouche, D
影响因子：
7
作者：
Lin, Jane M.;Collins, Patrick J.;Weng, Zhiping
通讯作者：
Weng, Zhiping
影响因子：
254.7
作者：
Landis, SH;Murray, T;Wingo, PA
通讯作者：
Wingo, PA