Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase

Xiao Jian Sun, Ju Wei, Xin Yan Wu, Ming Hu, Lan Wang, Hai Hong Wang, Qing Hua Zhang, Sai Juan Chen, Qiu Hua Huang, Zhu Chen

Research output: Contribution to journalArticlepeer-review

161 Scopus citations


Histone methylation plays an important role in eukaryotic transcriptional regulation. A number of histone methyltransferases (HMTases) with distinct functions have been identified. The HSPC069/HYPB gene was originally isolated from the human hematopoietic stem/progenitor cells (HSPCs), and it was also identified as a huntingtin interacting protein, implicated in the pathogenesis of Huntington disease (HD). However, its biochemical function is poorly understood. Here we report the structural and functional characterization of the huntingtin interacting protein B (HYPB). 1) The triplicate AWS-SET-PostSET domains mediate a histone H3 lysine 36 specific HMTase activity. 2) A low charged region that is rich in glutamine and proline has been characterized as a novel transcriptional activation domain. The structural features of this region are evolutionarily conserved in vertebrates. 3) Coimmunoprecipitation assays indicate that HYPB protein associates with hyperphosphorylated RNA polymerase II (RNAPII) but not the unphosphorylated form. Furthermore, the RNAPII-association region of HYPB protein has been identified to encompass the C-terminal 142 amino acids. Thus, our results suggest that HYPB HMTase may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of HD.

Original languageEnglish (US)
Pages (from-to)35261-35271
Number of pages11
JournalJournal of Biological Chemistry
Issue number42
StatePublished - Oct 21 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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