Wiley E A, Ohba R, Yao M C, Allis C D
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Mol Cell Biol. 2000 Nov;20(22):8319-28. doi: 10.1128/MCB.20.22.8319-8328.2000.
A clear relationship exists between histone acetylation and transcriptional output, the balance of which is conferred by opposing histone acetyltransferases (HATs) and histone deacetylases (HDACs). To explore the role of HDAC activity in determining the transcriptional competency of chromatin, we have exploited the biological features of Tetrahymena as a model. Each vegetative cell contains two nuclei: a somatic, transcriptionally active macronucleus containing hyperacetylated chromatin and a transcriptionally silent, germ line micronucleus containing hypoacetylated histones. Using a PCR-based strategy, a deacetylase gene (named THD1) encoding a homolog of the yeast HDAC Rpd3p was cloned. Thd1p deacetylates all four core histones in vitro. It resides exclusively in the macronucleus during vegetative growth and is asymmetrically distributed to developing new macronuclei early in their differentiation during the sexual pathway. Together, these data are most consistent with a potential role for Thd1p in transcriptional regulation and suggest that histone deacetylation may be important for the differentiation of micronuclei into macronuclei during development.
组蛋白乙酰化与转录输出之间存在明确的关系,而这种平衡是由相互对立的组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)赋予的。为了探究HDAC活性在决定染色质转录能力中的作用,我们利用了四膜虫的生物学特性作为模型。每个营养细胞包含两个细胞核:一个体细胞的、转录活跃的大核,其染色质高度乙酰化;以及一个转录沉默的种系小核,其组蛋白乙酰化程度较低。采用基于PCR的策略,克隆了一个编码酵母HDAC Rpd3p同源物的去乙酰化酶基因(命名为THD1)。Thd1p在体外可使所有四种核心组蛋白去乙酰化。在营养生长期间,它仅存在于大核中,并且在有性生殖途径中,在新大核分化早期不对称地分布到发育中的新大核中。这些数据综合起来,最符合Thd1p在转录调控中的潜在作用,并表明组蛋白去乙酰化可能对发育过程中小核向大核的分化很重要。