title: Structural insights into histone demethylation by JMJD2 family members.
abstract: Posttranslational modifications of histones regulate chromatin structure and gene expression. Histone demethylases, members of a newly emerging transcription-factor family, remove methyl groups from the lysine residues of the histone tails and thereby regulate the transcriptional activity of target genes. JmjC-domain-containing proteins have been predicted to be demethylases. For example, the JmjC-containing protein JMJD2A has been characterized as a H3-K9me3- and H3-K36me3-specific demethylase. Here, structures of the catalytic-core domain of JMJD2A with and without alpha-ketoglutarate in the presence of Fe2+ have been determined by X-ray crystallography. The structure of the core domain, consisting of the JmjN domain, the JmjC domain, the C-terminal domain, and a zinc-finger motif, revealed the unique elements that form a potential substrate binding pocket. Sited-directed mutagenesis in conjunction with demethylase activity assays allowed us to propose a molecular model for substrate selection by the JMJD2 histone demethylase family.
authors: Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors: Zhongzhou
authors: Z
authors: Chen
authors: Jianye
authors: J
authors: Zang
authors: Johnathan
authors: J
authors: Whetstine
authors: Xia
authors: X
authors: Hong
authors: Foteini
authors: F
authors: Davrazou
authors: Tatiana G
authors: TG
authors: Kutateladze
authors: Michael
authors: M
authors: Simpson
authors: Qilong
authors: Q
authors: Mao
authors: Cheol-Ho
authors: CH
authors: Pan
authors: Shaodong
authors: S
authors: Dai
authors: James
authors: J
authors: Hagman
authors: Kirk
authors: K
authors: Hansen
authors: Yang
authors: Y
authors: Shi
authors: Gongyi
authors: G
authors: Zhang