Davis Penny K, Brackmann Rainer K
Division of Hematology/Oncology, Department of Medicine, University of California at Irvine, Irvine, California 92697, USA.
Cancer Biol Ther. 2003 Jan-Feb;2(1):22-9. doi: 10.4161/cbt.189.
The fate of the cell relies on a delicate balance between gene expression and repression. The transcriptional control of the genome is maintained not only by transcription factors but also chromatin remodeling proteins. The purpose of the chromatin remodeling proteins is to alter the nucleosome architecture such that genes are exposed to or hidden from the transcriptional machinery. The nucleosome can be restructured by two mechanisms: 1. the movement of nucleosomes along DMA which is carried out by ATP-dependent chromatin remodeling complexes; and 2. the modification of core histones by histone acetyltransferases, deactylases, methyltrans-ferases, and kinases. Since these chromatin remodeling proteins play an essential role in transcriptional regulation, it is not surprising that they have been linked to cancer. In this review, we provide a general overview on chromatin remodeling and describe known genetic alterations of chromatin remodeling proteins in human cancers. We also discuss potential other, as yet unexplored strategies that cancers might take to manipulate the chromatin remodeling machinery.
细胞的命运取决于基因表达与抑制之间的微妙平衡。基因组的转录调控不仅由转录因子维持,还由染色质重塑蛋白维持。染色质重塑蛋白的作用是改变核小体结构,使基因暴露于转录机制或对转录机制隐藏。核小体可通过两种机制进行重构:1. 核小体沿DNA移动,这由依赖ATP的染色质重塑复合物完成;2. 核心组蛋白被组蛋白乙酰转移酶、脱乙酰酶、甲基转移酶和激酶修饰。由于这些染色质重塑蛋白在转录调控中起重要作用,它们与癌症相关也就不足为奇了。在本综述中,我们对染色质重塑进行了总体概述,并描述了人类癌症中已知的染色质重塑蛋白的基因改变。我们还讨论了癌症可能用于操纵染色质重塑机制的其他潜在的、尚未探索的策略。