Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast

Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast
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DOI:
10.1101/gad.1395506
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发表时间:
2006-03-15
影响因子:
10.5
通讯作者:
Grunstein, M
Grunstein, M
中科院分区:
生物学1区
文献类型:
--
作者:
Millar, CB;Xu, F;Grunstein, M

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组蛋白变体及其翻译后修饰有助于调节染色体功能。Htz1是一种进化保守的H_2A变异体,存在于酿酒酵母中的几个启动子中。在这项研究中,我们对酵母中的Htz1及其修饰进行了全基因组分析。通过质谱分析,我们确定Htz1在其N-末端的Lys 3、Lys 8、Lys 10和Lys 14上是乙酰化的,其中K14是乙酰化最丰富的位置。然后使用芯片和微阵列分析来比较Htz1-K14乙酰化与Htz1全基因组的位置。这些数据表明,虽然Htz1优先与抑制基因的启动子相关,但K14乙酰化在活性基因的启动子处丰富,并需要两个已知的组蛋白乙酰转移酶,Gcn5和Esa1。为了支持我们的全基因组分析,我们发现Htz1的乙酰化赖氨酸是其在PHO5重排后的核小体重组过程中完全沉积所必需的。由于Htz1的大部分乙酰化发生在活跃的启动子上,已知核小体在活性启动子上被分解,我们的数据证明了Htz1的重新组装是一个动态过程,在这个过程中,Htz1的重新组装是由其在转录过程中的启动子上的乙酰化来调节的。
Histone variants and their post-translational modifications help regulate chromosomal functions. Htz1 is an evolutionarily conserved H2A variant found at several promoters in the yeast Saccharomyces cerevisiae. In this study, we undertook a genome-wide analysis of Htz1 and its modifications in yeast. Using mass spectrometric analysis, we determined that Htz1 is acetylated at Lys 3, Lys 8, Lys 10, and Lys 14 within its N-terminal tail, with K14 being the most abundant acetylated site. ChIP and microarray analysis were then used to compare the location of Htz1-K14 acetylation to that of Htz1 genome-wide. The data presented here demonstrate that while Htz1 is associated preferentially with the promoters of repressed genes, K14 acetylation is enriched at the promoters of active genes, and requires two known histone acetyltransferases, Gcn5 and Esa1. In support of our genome-wide analysis, we found that the acetylatable lysines of Htz1 are required for its full deposition during nucleosome reassembly upon repression of PHO5. Since the majority of Htz1 acetylation is seen at active promoters, where nucleosomes are known to be disassembled, our data argue for a dynamic process in which reassembly of Htz1 is regulated by its acetylation at promoters during transcription.