Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression.
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.
Kim
Sung-Hak
SH
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul, Republic of Korea.
Park
Jinah
J
Choi
Moon-Chang
MC
Kim
Hwang-Phill
HP
Park
Jung-Hyun
JH
Jung
Yeonjoo
Y
Lee
Ju-Hee
JH
Oh
Do-Youn
DY
Im
Seock-Ah
SA
Bang
Yung-Jue
YJ
Kim
Tae-You
TY
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
D004248:DNA (Cytosine-5-)-Methyltransferases; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097584:DNA Methyltransferase 3B; C484404:ZHX1 protein, human