Chromatin remodeling and epigenetic regulation of the CrabpI gene in adipocyte differentiation

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)206-212
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1821
Issue number1
DOIs
StatePublished - Jan 2012

Bibliographical note

Funding Information:
This study was supported in part by NIH grants DK60543 , DK060543-07S1 , DK56735 , DK056735-09S1 , DA11210 , K02-DA16128 and the Distinguished McKnight University Professorship (L.-N. W.)

Keywords

  • CRABPI
  • Chromatin remodeling
  • RIP140. TRAP220
  • Retinoic acid
  • Thyroid hormone

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