title: Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Lin
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.forename: Pu
authors.initials: P
authors.lastname: Pu
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.forename: Hailei
authors.initials: H
authors.lastname: Mao
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Lulu
authors.initials: L
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xu
authors.forename: Charlie Degui
authors.initials: CD
authors.lastname: Chen
mesh_terms: 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
chemical_list: D029742:Caenorhabditis elegans Proteins; D006657:Histones; C553255:JMJD-1.2 protein, C elegans; D056484:Jumonji Domain-Containing Histone Demethylases