Structural insights into histone demethylation by JMJD2 family members.
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.
Chen
Zhongzhou
Z
Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Zang
Jianye
J
Whetstine
Johnathan
J
Hong
Xia
X
Davrazou
Foteini
F
Kutateladze
Tatiana G
TG
Simpson
Michael
M
Mao
Qilong
Q
Pan
Cheol-Ho
CH
Dai
Shaodong
S
Hagman
James
J
Hansen
Kirk
K
Shi
Yang
Y
Zhang
Gongyi
G