Lafon A, Chang C S, Scott E M, Jacobson S J, Pillus L
Section of Molecular Biology, Division of Biological Sciences, UCSD Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Oncogene. 2007 Aug 13;26(37):5373-84. doi: 10.1038/sj.onc.1210606.
The MYST family of histone acetyltransferases (HATs) was initially defined by human genes with disease connections and by yeast genes identified for their role in epigenetic transcriptional silencing. Since then, many new MYST genes have been discovered through genetic and genomic approaches. Characterization of the complexes through which MYST proteins act, regions of the genome to which they are targeted and biological consequences when they are disrupted, all deepen the connections of MYST proteins to development, growth control and human cancers. Many of the insights into MYST family function have come from studies in model organisms. Herein, we review functions of two of the founding MYST genes, yeast SAS2 and SAS3, and the essential yeast MYST ESA1. Analysis of these genes in yeast has defined roles for MYST proteins in transcriptional activation and silencing, and chromatin-mediated boundary formation. They have further roles in DNA damage repair and nuclear integrity. The observation that MYST protein complexes share subunits with other HATs, histone deacetylases and other key nuclear proteins, many with connections to human cancers, strengthens the idea that coordinating distinct chromatin modifications is critical for regulation.
组蛋白乙酰转移酶（HATs）的MYST家族最初是由与疾病相关的人类基因以及因其在表观遗传转录沉默中的作用而鉴定出的酵母基因所定义的。从那时起，通过遗传和基因组方法发现了许多新的MYST基因。对MYST蛋白发挥作用的复合物、它们靶向的基因组区域以及它们被破坏时的生物学后果进行表征，都加深了MYST蛋白与发育、生长控制和人类癌症之间的联系。对MYST家族功能的许多见解都来自对模式生物的研究。在此，我们综述了两个最初的MYST基因，酵母SAS2和SAS3，以及酵母必需的MYST基因ESA1的功能。在酵母中对这些基因的分析确定了MYST蛋白在转录激活和沉默以及染色质介导的边界形成中的作用。它们在DNA损伤修复和核完整性方面还有进一步的作用。MYST蛋白复合物与其他HATs、组蛋白去乙酰化酶和其他关键核蛋白共享亚基，其中许多与人类癌症有关，这一观察结果强化了这样一种观点，即协调不同的染色质修饰对于调控至关重要。
