真核生物染色質的組蛋白末端會發生多種化學修飾（包括乙醯化和甲基化修飾等），是真核生物細胞隨環境變化而改變基因表達譜式的重要調控方式。之前的研究發現組蛋白H3K4甲基化分布於基因的啟動子區，對基因轉錄主要起正調控作用。然而有研究表明H3K4甲基化對某些基因表達起到抑制作用，其分子機制有待闡釋。
2011年6月6日的《Molecular and Cellular Biology》在線發表了周金秋研究組揭示組蛋白H3K4甲基化抑制基因轉錄機制的文章。研究生王珊珊等以釀酒酵母的PHO5為模式基因，發現甲基化的組蛋白H3K4通過招募組蛋白去乙醯化酶Rpd3L複合物，對PHO5基因的啟動子區的組蛋白H3去乙醯化，從而穩定核小體的結構並抑制PHO5基因的轉錄的起始。他們的研究揭示了組蛋白H3K4甲基化抑制轉錄的一種新機制，表明真核生物細胞內組蛋白末端的同一種共價修飾在基因組不同的位置所發揮的功能是不同的。
該研究獲得了國家科技部和國家自然科學基金委的經費資助。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
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周金秋研究員：端粒——穩定線性染色體的末端結構
http://www.bioon.com/trends/comment/411939.shtml