Structural Insights into Histone Demethylation by JMJD2 Family Members

Zhongzhou Chen, Jianye Zang, Johnathan Whetstine, Xia Hong, Foteini Davrazou, Tatiana G. Kutateladze, Michael Simpson, Qilong Mao, Cheol Ho Pan, Shaodong Dai, James Hagman, Kirk Hansen, Yang Shi, Gongyi Zhang

Research output: Contribution to journalArticlepeer-review

322 Scopus citations


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.

Original languageEnglish
Pages (from-to)691-702
Number of pages12
Issue number4
StatePublished - May 19 2006


  • Amino Acid Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • DNA-Binding Proteins/chemistry
  • Histones/metabolism
  • Methylation
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptides/chemistry
  • Point Mutation
  • Protein Conformation
  • Sequence Alignment
  • Transcription Factors/chemistry


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