화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.443, No.2, 489-494, 2014
Reciprocal regulation of LXR alpha activity by ASXL1 and ASXL2 in lipogenesis
Liver x receptor alpha (LXR alpha), 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 LXR alpha activity. We found that ASXL1 suppressed ligand-induced LXR alpha transcriptional activity, whereas ASXL2 increased LXR alpha activity through direct interaction in the presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand-dependent recruitment of ASXLs to ABCA1 promoters, like LXR alpha. 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 LXR alpha. (C) 2013 Elsevier Inc. All rights reserved.