肝X受体
生物
核受体
染色质免疫沉淀
转录调控
转录因子
染色质
细胞生物学
视黄醇X受体
基因表达调控
发起人
基因表达
遗传学
基因
作者
Ana Ramón-Vázquez,Juan Vladimir de la Rosa,Carlos Tabraue,Félix López,B.N. Díaz-Chico,Lisardo Boscá,Peter Tontonoz,Susana Alemany,Antonio Castrillo
摘要
The liver X receptors α and β (LXRα and LXRβ) are oxysterol-activated transcription factors that coordinately regulate gene expression that is important for cholesterol and fatty acid metabolism. In addition to their roles in lipid metabolism, LXRs participate in the transcriptional regulation of macrophage activation and are considered potent regulators of inflammation. LXRs are highly similar, and despite notable exceptions, most of their reported functions are substantially overlapping. However, their individual genomic distribution and transcriptional capacities have not been characterized. Here, we report a macrophage cellular model expressing equivalent levels of tagged LXRs. Analysis of data from chromatin immunoprecipitation coupled with deep sequencing revealed that LXRα and LXRβ occupy both overlapping and exclusive genomic regulatory sites of target genes and also control the transcription of a receptor-exclusive set of genes. Analysis of genomic H3K27 acetylation and mRNA transcriptional changes in response to synthetic agonist or antagonist treatments revealed a putative mode of pharmacologically independent regulation of transcription. Integration of microarray and sequencing data enabled the description of three possible mechanisms of LXR transcriptional activation. Together, these results contribute to our understanding of the common and differential genomic actions of LXRs and their impact on biological processes in macrophages.
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