Lehrmann Heike, Pritchard Linda Louise, Harel-Bellan Annick
CNRS UPR 9079, Institut André Lwoff, Villejuif, France.
Adv Cancer Res. 2002;86:41-65. doi: 10.1016/s0065-230x(02)86002-x.
Histone acetylation and deacetylation are chromatin-modifying processes that have fundamental importance for transcriptional regulation. Transcriptionally active chromatin regions show a high degree of histone acetylation, whereas deacetylation events are generally linked to transcriptional silencing. Many of the acetylating and deacetylating enzymes were originally identified as transcriptional coactivators or repressors. Their histone-modifying enzymatic activity was discovered more recently, opening up a whole new area of research. Histone acetyltransferases such as CREB-binding protein (CBP) and PCAF are involved in processes as diverse as promoting cell cycle progression and regulating differentiation. A controlled balance between histone acetylation and deacetylation seems to be essential for normal cell growth. Both histone acetyltransferases and deacetylases are involved in the development of diseases, including neurodegenerative disorders and cancer. Treatments that target these enzymes are already under clinical investigation.
组蛋白乙酰化和去乙酰化是对转录调控具有根本重要性的染色质修饰过程。转录活跃的染色质区域显示出高度的组蛋白乙酰化，而去乙酰化事件通常与转录沉默相关。许多乙酰化和去乙酰化酶最初被鉴定为转录共激活因子或抑制因子。它们的组蛋白修饰酶活性是最近才被发现的，这开辟了一个全新的研究领域。诸如CREB结合蛋白（CBP）和PCAF等组蛋白乙酰转移酶参与了促进细胞周期进程和调节分化等多种过程。组蛋白乙酰化和去乙酰化之间的受控平衡似乎对正常细胞生长至关重要。组蛋白乙酰转移酶和去乙酰化酶都参与了包括神经退行性疾病和癌症在内的疾病发展过程。针对这些酶的治疗方法已在临床研究中。
