title: Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression.
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.
authors.affiliation: National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul, Republic of Korea.
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.forename: Jinah
authors.initials: J
authors.lastname: Park
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Choi
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yeonjoo
authors.initials: Y
authors.lastname: Jung
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097584:DNA Methyltransferase 3B; C484404:ZHX1 protein, human