Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis
- Department of Bioscience and Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747 (Korea, Republic of)
- Department of Molecular Biology, BK21 Graduate Program, Dankook University, Gyeonggi-do 448-701 (Korea, Republic of)
- The Catholic University Liver Research Center and WHO Collaborating Center of Viral Hepatitis, The Catholic University, College of Medicine, Seoul 137-701 (Korea, Republic of)
Highlights: •ASXL1 and ASXL2 directly interact with ligand-bound LXRα. •Ligand-induced LXRα activity is repressed by ASXL1 and activated by ASXL2. •ASXL1 and ASXL2 bind to the LXRE of the LXRα target promoter. •ASXL1 and ASXL2 reciprocally regulate lipogenesis in liver cells. -- Abstract: Liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the expression of genes associated with hepatic lipogenesis. The additional sex comb-like (ASXL) family was postulated to regulate chromatin function. Here, we investigate the roles of ASXL1 and ASXL2 in regulating LXRα activity. We found that ASXL1 suppressed ligand-induced LXRα transcriptional activity, whereas ASXL2 increased LXRα activity through direct interaction in the presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand-dependent recruitment of ASXLs to ABCA1 promoters, like LXRα. Knockdown studies indicated that ASXL1 inhibits, while ASXL2 increases, lipid accumulation in H4IIE cells, similar to their roles in transcriptional regulation. We also found that ASXL1 expression increases under fasting conditions, and decreases in insulin-treated H4IIE cells and the livers of high-fat diet-fed mice. Overall, these results support the reciprocal role of the ASXL family in lipid homeostasis through the opposite regulation of LXRα.
- OSTI ID:
- 22242258
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 443, Issue 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase
Salvianolic acid B accelerated ABCA1-dependent cholesterol efflux by targeting PPAR-γ and LXRα