Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression

Biochem Biophys Res Commun. 2007 Apr 6;355(2):318-23. doi: 10.1016/j.bbrc.2007.01.187. Epub 2007 Feb 8.

Abstract

DNA methyltransferases (DNMT) 3B is a de novo DNMT that represses transcription independent of DNMT activity. In order to gain a better insight into DNMT3B-mediated transcriptional repression, we performed a yeast two-hybrid analysis using DNMT3B as a bait. Of the various binding candidates, ZHX1, a member of zinc-finger and homeobox protein, was found to interact with DNMT3B in vivo and in vitro. N-terminal PWWP domain of DNMT3B was required for its interaction with homeobox motifs of ZHX1. ZHX1 contains nuclear localization signal at C-terminal homeobox motif, and both ZHX1 and DNMT3B were co-localized in nucleus. Furthermore, we found that ZHX1 enhanced the transcriptional repression mediated by DNMT3B when DNMT3B is directly targeted to DNA. These results showed for the first the direct linkage between DNMT and zinc-fingers homeoboxes protein, leading to enhanced gene silencing by DNMT3B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • Genes, Homeobox
  • Homeodomain Proteins / metabolism*
  • Humans
  • Microscopy, Fluorescence
  • Protein Binding
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • ZHX1 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3B