TY - JOUR
T1 - Structural Insights into Histone Demethylation by JMJD2 Family Members
AU - Chen, Zhongzhou
AU - Zang, Jianye
AU - Whetstine, Johnathan
AU - Hong, Xia
AU - Davrazou, Foteini
AU - Kutateladze, Tatiana G.
AU - Simpson, Michael
AU - Mao, Qilong
AU - Pan, Cheol Ho
AU - Dai, Shaodong
AU - Hagman, James
AU - Hansen, Kirk
AU - Shi, Yang
AU - Zhang, Gongyi
PY - 2006/5/19
Y1 - 2006/5/19
N2 - 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 α-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.
AB - 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 α-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.
KW - Amino Acid Sequence
KW - Catalytic Domain
KW - Crystallography, X-Ray
KW - DNA-Binding Proteins/chemistry
KW - Histones/metabolism
KW - Methylation
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Mutagenesis, Site-Directed
KW - Peptides/chemistry
KW - Point Mutation
KW - Protein Conformation
KW - Sequence Alignment
KW - Transcription Factors/chemistry
UR - http://www.scopus.com/inward/record.url?scp=33646505724&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2006.04.024
DO - 10.1016/j.cell.2006.04.024
M3 - Article
C2 - 16677698
AN - SCOPUS:33646505724
SN - 0092-8674
VL - 125
SP - 691
EP - 702
JO - Cell
JF - Cell
IS - 4
ER -