title: Involvement of liver X receptor alpha in histone modifications across the target fatty acid synthase gene.
abstract: The liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, has been shown to regulate the expression of the fatty acid synthase (FAS) gene through direct interaction with the FAS promoter. However, its regulation of gene expression is not completely understood. Histone modifications and chromatin remodeling are closely linked to transcriptional activation of genes. In the present study, we examined the effect of LXRα activation or silencing on histone modifications (i.e., acetylation, methylation, and phosphorylation) across the FAS gene, with the aim to investigate whether LXRα could regulate its target gene expression at the epigenetic level. The addition of LXR agonist T0901317 or ectopic expression of LXRα stimulated the FAS transcription, which was coupled with increased levels of histones H3 and H4 acetylation and H3 phosphorylation and methylation at the LXR response element (LXRE). LXR ligation or overexpression induced distinct histone modification patterns at the distal region 2,272 bp upstream from the transcription start site (TSS) and TSS of the FAS gene. Moreover, RNA interference-mediated downregulation of LXRα impaired the histone acetylation and methylation but not phosphorylation on the FAS gene. In conclusion, we provide evidence that LXRα ligation-mediated transcriptional activation of the FAS gene is associated with LXRα-dependent histone acetylation and methylation rather than phosphorylation on this target gene.
authors.affiliation: Department of Digestive Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Huihong
authors.initials: H
authors.lastname: Yu
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Jinjun
authors.initials: J
authors.lastname: Guo
authors.forename: Lili
authors.initials: L
authors.lastname: Zheng
authors.forename: Mingli
authors.initials: M
authors.lastname: Peng
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Xiang
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000235:genetics* / Q000378:metabolism*; D006657:Histones; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008745:Methylation; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D034622:RNA Interference; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064429:Fatty Acid Synthases; D006657:Histones; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides