| First Author | Londoño Gentile T | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 19 | Pages | 3864-78 |
| PubMed ID | 23897429 | Mgi Jnum | J:205021 |
| Mgi Id | MGI:5543880 | Doi | 10.1128/MCB.01495-12 |
| Citation | Londono Gentile T, et al. (2013) DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation. Mol Cell Biol 33(19):3864-78 |
| abstractText | During adipocyte differentiation, significant epigenomic changes occur in association with the implementation of the adipogenic program. We have previously shown that histone acetylation increases during differentiation in a manner dependent on acetyl coenzyme A (acetyl-CoA) production by the enzyme ATP-citrate lyase (ACL). Whether ACL regulates nuclear targets in addition to histones during differentiation is not clear. In this study, we report that DNA methyltransferase 1 (DNMT1) levels in adipocytes are controlled in part by ACL and that silencing of DNMT1 can accelerate adipocyte differentiation. DNMT1 gene expression is induced early in 3T3-L1 adipocyte differentiation during mitotic clonal expansion and is critical for maintenance of DNA and histone H3K9 methylation patterns during this period. In the absence of DNMT1, adipocyte-specific gene expression and lipid accumulation occur precociously. Later in differentiation, DNMT1 levels decline in an ACL-dependent manner. ACL-mediated suppression of DNMT1 occurs at least in part by promoting expression of microRNA 148a (miR-148a), which represses DNMT1. Ectopic expression of miR-148a accelerates differentiation under standard conditions and can partially rescue a hypermethylation-mediated differentiation block. The data suggest a role for DNMT1 in modulating the timing of differentiation and describe a novel ACL-miR-148a-dependent mechanism for regulating DNMT1 during adipogenesis. |
