PMID:24321552

Citation	Park, UH, Seong, MR, Kim, EJ, Hur, W, Kim, SW, Yoon, SK and Um, SJ (2014) Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis. Biochem. Biophys. Res. Commun. 443:489-94
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.
Links	PubMed Online version:10.1016/j.bbrc.2013.11.124
Keywords	Animals; Cell Line; Gene Expression Regulation; Hepatocytes/metabolism; Lipogenesis/physiology; Mice; Orphan Nuclear Receptors/metabolism; Rats; Repressor Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:A0A0G2JU33		GO:0010888: negative regulation of lipid storage	ECO:0000315:		P		Figure 4B shows that ASXL1 knockdown increased intracellular lipid accumulation after cells were treated with 0.1 mM palmitate.	complete CACAO 11502
RAT:D3Z8N9		GO:0010884: positive regulation of lipid storage	ECO:0000315:		P		Figure 4B shows that ASXL2 knockdown significantly blocked intracellular lipid accumulation after the addition of 0.1 mM palmitate.	complete CACAO 11503

References

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