| First Author | Krebs CJ | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 2 | Pages | 221-32 |
| PubMed ID | 24190968 | Mgi Jnum | J:207685 |
| Mgi Id | MGI:5559382 | Doi | 10.1128/MCB.00875-13 |
| Citation | Krebs CJ, et al. (2014) The KRAB zinc finger protein RSL1 modulates sex-biased gene expression in liver and adipose tissue to maintain metabolic homeostasis. Mol Cell Biol 34(2):221-32 |
| abstractText | Kruppel-associated box zinc finger proteins (KRAB-ZFPs) are a huge family of vertebrate-specific repressors that modify gene expression in an epigenetic manner. Despite a well-defined repression mechanism, few biological roles or gene targets of KRAB-ZFP are known. Regulator of sex-limitation 1 (RSL1) is a mouse KRAB-ZFP that enforces male-predominant expression in the liver, affecting body mass and pubertal timing. Here we show that female but not male Rsl1(-/-) mice gain more weight than wild-type mice on a high-fat diet (HFD) and that key liver and white adipose tissue (WAT) metabolic genes are altered in both Rsl1(-/-) sexes in response to dietary stress. Expression profiling of Rsl1-sensitive genes in liver and WAT indicates that RSL1 accentuates sex-biased gene expression in liver but greatly diminishes it in WAT. RSL1 expression solely in liver is sufficient to limit diet-induced weight gain and suppress lipogenic genes in WAT, indicating that RSL1 balances metabolism via liver-to-adipose-tissue communication. RSL1's effects on adult physiology exemplify a significant modulatory capacity of KRAB-ZFPs, in the absence of which there is widespread metabolic dysregulation. This ability to buffer against gene expression noise, coupled with extensive individual genetic variation, highlights the enormous potential of KRAB-Zfp genes as candidate risk factors for complex diseases. |
