The Mechanism of H3K4 Methylation-mediated Transcription Repression

Histone modification plays important roles in transcription regulation. Histone H3K4 tri-methylation (H3K4-me3), catalyzed by the histone methytransferase Set1, is predominantly associated with actively transcribed genes. Nevertheless, several lines of evidence have highlighted the repressive role of histone H3K4 methylation in gene transcription, and the underlying mechanism remains elusive. Recently, researchers in Dr. ZHOU Jinqiu’s lab, at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, using yeast PHO5 gene as a model, elucidated the molecular mechanism by which Set1-mediated H3K4me represses gene expression.

 

They found that histone H3K4 was hypermethylated at the PHO5 promoter independently of the activation state. Elimination of H3K4me did not affect the recruitment of the transcription factors Pho2 and Pho4, but rather led to a relatively open chromatin structure of the PHO5 promoter, suggesting that Set1-mediated H3K4me inhibits PHO5M transcription by chromatin-based mechanism. They also found that the histone deacetylase complex Rpd3L was targeted to PHO5 promoter by H3K4 di- and tri-methylation and mediated the function of Set1. Although Rpd3 deacetylated both H3 and H4 at the PHO5 promoter, Set1 appeared to be specifically affect H3 deacetylation.

 

This work entitled "Histone H3 Lysine 4 Hypermethylation Prevents Aberrant Nucleosome Remodeling at the PHO5 Promoter " was published online in Molecular and Cellular Biology on June 6th, 2011.

 

This study was supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China.

 

AUTHOR CONTACT:

ZHOU Jinqiu

The State Key laboratory of Molecular Biology

Institute of Biochemistry and Cell Biology

Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Shanghai, China

Phone: 86-21- 54921076

E-mail: zhoulab@sibs.ac.cn