Protein phosphatase PP1 is required for normal DNA methylation in Neurospora
Protein phosphatase PP1 is required for normal DNA methylation in Neurospora
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DOI：
10.1101/gad.1738008
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发表时间：
2008-12-15
影响因子：
10.5
通讯作者：
Selker, Eric U.
中科院分区：
文献类型：
--
作者：
Adhvaryu, Keyur K.;Selker, Eric U.
组蛋白的共价修饰整合了细胞内和细胞外的信号来调节基因组。H3Lys 9甲基化(H3K9me)可以引导异染色质的形成和DNA甲基化，而H3Ser10(H3S10p)的磷酸化则驱动基因激活和染色体凝聚。为了研究粗糙脉孢菌中H3S10p、H3K9me和DNA甲基化之间的关系，我们构建并测试了可能的H3S10磷酸酶PP1的突变体。1个PP1损伤的突变体显示H3S10p增加，H3K9和DNA甲基化选择性降低。同样，H3S10的氨基酸替换取消了H3K9和DNA的甲基化。因此，某些基因座的DNA甲基化需要PP1对H3S10进行去磷酸化。
Covalent modifications of histones integrate intracellular and extracellular cues to regulate the genome. H3 Lys 9 methylation (H3K9me) can direct heterochromatin formation and DNA methylation, while phosphorylation of H3 Ser 10 (H3S10p) drives gene activation and chromosome condensation. To examine the relationship between H3S10p, H3K9me, and DNA methylation in Neurospora crassa, we built and tested mutants of the putative H3S10 phosphatase, PP1. A PP1-impaired mutant showed increased H3S10p and selective reduction of methylation of H3K9 and DNA. Similarly, amino acid substitutions of H3S10 abolished methylation of H3K9 and DNA. Thus, H3S10 dephosphorylation by PP1 is required for DNA methylation of some loci.