Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans.
H3K9me2 and H3K27me2 are important epigenetic marks associated with transcription repression, while H3K4me3 is associated with transcription activation. It has been shown that active and repressive histone methylations distribute in a mutually exclusive manner, but the underlying mechanism was poorly understood. Here we identified ceKDM7A, a PHD (plant homeodomain)- and JmjC domain-containing protein, as a histone demethylase specific for H3K9me2 and H3K27me2. We further demonstrated that the PHD domain of ceKDM7A bound H3K4me3 and H3K4me3 co-localized with ceKDM7A at the genome-wide level. Disruption of the PHD domain binding to H3K4me3 reduced the demethylase activity in vivo, and loss of ceKDM7A reduced the expression of its associated target genes. These results indicate that ceKDM7A is recruited to the promoter to demethylate H3K9me2 and H3K27me2 and activate gene expression through the binding of the PHD domain to H3K4me3. Thus, our study identifies a dual-specificity histone demethylase and provides novel insights into the regulation of histone methylation.
Lin
Hanqing
H
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
Wang
Yiqin
Y
Wang
Yanru
Y
Tian
Feng
F
Pu
Pu
P
Yu
Yi
Y
Mao
Hailei
H
Yang
Ying
Y
Wang
Ping
P
Hu
Lulu
L
Lin
Yan
Y
Liu
Yi
Y
Xu
Yanhui
Y
Chen
Charlie Degui
CD
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D029742:Caenorhabditis elegans Proteins; D006657:Histones; C553255:JMJD-1.2 protein, C elegans; D056484:Jumonji Domain-Containing Histone Demethylases