ArticleMolecular and cellular biology2014
The KRAB zinc finger protein RSL1 modulates sex-biased gene expression in liver and adipose tissue to maintain metabolic homeostasis.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
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- Identification of a TRBD zinc finger-interacting protein in Giardia duodenalis and its regulation of telomerase.Parasites & vectors · 2019Article
- Tissue-SpecificGenetics · 2019Article
- MicroRNA-339 inhibits human hepatocellular carcinoma proliferation and invasion via targeting ZNF689.Drug design, development and therapy · 2019Article
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- ZNF259 promotes breast cancer cells invasion and migration via ERK/GSK3β/snail signaling.Cancer management and research · 2018Article
- Genetic Basis for Sex Differences in Obesity and Lipid Metabolism.Annual review of nutrition · 2017Review
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- Genome-wide association study of body mass index in subjects with alcohol dependence.Addiction biology · 2017Article
- ZNF545 suppresses human hepatocellular carcinoma growth by inhibiting NF-kB signaling.Genes & cancer · 2017Article
- Zinc finger proteins in cancer progression.Journal of biomedical science · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Krüppel-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.
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