Wei Li-Na
Department of Pharmacology, University of Minnesota Medical School, 6-122 Jackson Hall, 341 Church St. SE, Minneapolis, MN 55655, USA.
Biochim Biophys Acta. 2012 Jan;1821(1):206-12. doi: 10.1016/j.bbalip.2011.03.003. Epub 2011 Mar 22.
Retinoic acid (RA) acts by binding to nuclear RA receptors (RARs) to regulate a broad spectrum of downstream target genes in most cell types examined. In cytoplasm, RA binds specifically to cellular retinoic acid binding proteins I (CRABPI), and II. Although the function of CRABPI in animals remains the subject of debate, it is believed that CRABPI binding facilitates RA metabolism, thereby modulating the concentration of RA and the type of RA metabolites in cells. The basal promoter of the CrabpI gene is a housekeeping promoter that can be regulated by thyroid hormones (T3), DNA methylation, sphinganine, and ethanol acting on its upstream regulatory region. T3 regulation of CrabpI is mediated by the binding of thyroid hormone receptor (TR) to a TR response element (TRE) approximately 1 kb upstream of the basal promoter. Specifically, in the adipocyte differentiation process, T3 regulation is bimodal and closely associated with the cellular differentiation status: T3 activates CrabpI in predifferentiated cells (e.g., mesenchymal precursors or fibroblasts), but suppresses this gene once cells are committed to adipocyte differentiation. These disparate effects are functions of T3-triggered differential recruitment of coregulatory complexes in conjunction with chromatin looping/folding that alters the configuration of this genomic locus along adipocyte differentiation. Subsequent sliding, disassembly and reassembly of nucleosomes occur, resulting in specific changes in the conformation of the basal promoter chromatin at different stages of differentiation. This chapter summarizes studies illustrating the epigenetic regulation of CrabpI expression during adipocyte differentiation. Understanding the pathways regulating CrabpI in this specific context might help to illuminate the physiological role of CRABPI in vivo. This article is part of a special issue entitled: Retinoid and Lipid Metabolism.
视黄酸（RA）通过与核视黄酸受体（RARs）结合发挥作用，以调节大多数被检测细胞类型中的广泛下游靶基因。在细胞质中，RA特异性结合细胞视黄酸结合蛋白I（CRABPI）和II。尽管CRABPI在动物体内的功能仍存在争议，但人们认为CRABPI结合有助于RA代谢，从而调节细胞内RA的浓度和RA代谢物的类型。CrabpI基因的基础启动子是一个管家启动子，可受甲状腺激素（T3）、DNA甲基化、鞘氨醇和作用于其上游调控区域的乙醇的调节。CrabpI的T3调节是通过甲状腺激素受体（TR）与基础启动子上游约1 kb处的TR反应元件（TRE）结合介导的。具体而言，在脂肪细胞分化过程中，T3调节具有双峰性，且与细胞分化状态密切相关：T3在预分化细胞（如间充质前体或成纤维细胞）中激活CrabpI，但一旦细胞开始向脂肪细胞分化，该基因就会被抑制。这些不同的效应是T3触发的共调节复合物的差异募集与染色质环化/折叠共同作用的结果，染色质环化/折叠会改变该基因组位点在脂肪细胞分化过程中的构型。随后核小体发生滑动、解体和重新组装，导致基础启动子染色质在分化的不同阶段发生特定的构象变化。本章总结了说明脂肪细胞分化过程中CrabpI表达的表观遗传调控的研究。了解在这种特定背景下调节CrabpI的途径可能有助于阐明CRABPI在体内的生理作用。本文是名为：类视黄醇与脂质代谢的特刊的一部分。
