| First Author | Zhang Y | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 11 | Pages | 4850-60 |
| PubMed ID | 22362755 | Mgi Jnum | J:197706 |
| Mgi Id | MGI:5494360 | Doi | 10.1093/nar/gks159 |
| Citation | Zhang Y, et al. (2012) Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear receptor SHP. Nucleic Acids Res 40(11):4850-60 |
| abstractText | Dnmt1 is frequently overexpressed in cancers, which contributes significantly to cancer-associated epigenetic silencing of tumor suppressor genes. However, the mechanism of Dnmt1 overexpression remains elusive. Herein, we elucidate a pathway through which nuclear receptor SHP inhibits zinc-dependent induction of Dnmt1 by antagonizing metal-responsive transcription factor-1 (MTF-1). Zinc treatment induces Dnmt1 transcription by increasing the occupancy of MTF-1 on the Dnmt1 promoter while decreasing SHP expression. SHP in turn represses MTF-1 expression and abolishes zinc-mediated changes in the chromatin configuration of the Dnmt1 promoter. Dnmt1 expression is increased in SHP-knockout (sko) mice but decreased in SHP-transgenic (stg) mice. In human hepatocellular carcinoma (HCC), increased DNMT1 expression is negatively correlated with SHP levels. Our study provides a molecular explanation for increased Dnmt1 expression in HCC and highlights SHP as a potential therapeutic target. |
