Zhou Wenlai, Wang Xiangting, Rosenfeld Michael G
Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Int J Biochem Cell Biol. 2009 Jan;41(1):12-5. doi: 10.1016/j.biocel.2008.09.016. Epub 2008 Sep 26.
The precise molecular strategies that coordinate patterns of transcriptional response to specific signals is central for understanding normal development and disease. Precise control of transcriptional programs underlying metazoan development is modulated by enzymatically active coregulatory complexes, coupled with epigenetic strategies. Epigenetic modifications, particularly DNA methylation and covalent histone modifications, for instance acetylation, methylation, phosphorylation and ubiquitination, play an essential role in transcription regulation, chromatin remodeling, genome instability and X chromosome inactivation. Recently, the ubiquitinases and deubiquitinases responsible for histone H2A ubiquitination and deubiquitination have been identified and characterized. These studies suggest that histone H2A ubiquitination play important roles in many cellular events, such as transcription initiation and elongation, silencing, and DNA repair. Alteration of histone H2A ubiquitination modifications may contribute human diseases, such as cancer. In this review, we discuss enzymes involved in H2A ubiquitination/deubiquitination and that possible molecular mechanisms underlying histone H2A ubiquitination/deubiquitination in transcriptional regulation and DNA damage repair.
协调对特定信号的转录反应模式的精确分子策略对于理解正常发育和疾病至关重要。后生动物发育基础转录程序的精确控制由具有酶活性的共调节复合物以及表观遗传策略共同调节。表观遗传修饰，特别是DNA甲基化和共价组蛋白修饰，如乙酰化、甲基化、磷酸化和泛素化，在转录调控、染色质重塑、基因组不稳定和X染色体失活中起重要作用。最近，负责组蛋白H2A泛素化和去泛素化的泛素酶和去泛素酶已被鉴定和表征。这些研究表明，组蛋白H2A泛素化在许多细胞事件中起重要作用，如转录起始和延伸、沉默和DNA修复。组蛋白H2A泛素化修饰的改变可能导致人类疾病，如癌症。在本综述中，我们讨论了参与H2A泛素化/去泛素化的酶以及组蛋白H2A泛素化/去泛素化在转录调控和DNA损伤修复中的可能分子机制。
