真核生物染色质的组蛋白末端会发生多种化学修饰（包括乙酰化和甲基化修饰等），是真核生物细胞随环境变化而改变基因表达谱式的重要调控方式。之前的研究发现组蛋白H3K4甲基化分布于基因的启动子区，对基因转录主要起正调控作用。然而有研究表明H3K4甲基化对某些基因表达起到抑制作用，其分子机制有待阐释。

2011年6月6日的《Molecular and Cellular Biology》在线发表了周金秋研究组揭示组蛋白H3K4甲基化抑制基因转录机制的文章。研究生王珊珊等以酿酒酵母的PHO5为模式基因，发现甲基化的组蛋白H3K4通过招募组蛋白去乙酰化酶Rpd3L复合物，对PHO5基因的启动子区的组蛋白H3去乙酰化，从而稳定核小体的结构并抑制PHO5基因的转录的起始。他们的研究揭示了组蛋白H3K4甲基化抑制转录的一种新机制，表明真核生物细胞内组蛋白末端的同一种共价修饰在基因组不同的位置所发挥的功能是不同的。

该研究获得了国家科技部和国家自然科学基金委的经费资助。（生物谷Bioon.com）

生物谷推荐原文出处：

Molecular and Cellular Biology DOI:10.1128/MCB.05017-11

Histone H3 Lysine 4 Hypermethylation Prevents Aberrant Nucleosome Remodeling at the PHO5 Promoter

Shan-Shan Wang, Bo O. Zhou, and Jin-Qiu Zhou

Recent studies have highlighted the histone H3K4 methylation (H3K4me)-dependent transcriptional repression in Saccharomyces cerevisiae, however, the underlying mechanism remains inexplicit. Here, we reported that H3K4me inhibits the basal PHO5 transcription under high-phosphate conditions by suppressing nucleosome disassembly at the promoter. We found that derepression of the PHO5 promoter by SET1 deletion resulted in a labile chromatin structure, allowing more binding of RNA Pol II, but not the transactivators Pho2 and Pho4. We further showed that Pho23 and Cti6, two PHD-containing proteins, cooperatively anchored the Rpd3L complex to the H3K4-methylated PHO5 promoter. The deacetylation activity of Rpd3 on histone H3 was required for the function of Set1 at the PHO5 promoter. Taken together, our data suggest that Set1-mediated H3K4me suppresses nucleosome remodeling at the PHO5 promoter so as to reduce basal transcription of PHO5 under repressive conditions. We propose that the restriction of aberrant nucleosome remodeling contributes to strict control of gene transcription by the transactivators.