The nuclear receptor superfamily of steroid hormones and vitamin D gene regulation. An update.
Nuclear receptors bind to chromatin and seed formation of complexes comprising coregulators at the hormone response element. Nuclear receptors and coregulators can mediate chromatin remodeling, epigenetic modification, and ultimately gene expression. Chromatin immunoprecipitation has shown that nuclear receptors bind to chromatin throughout the genome, often at locations distant from the transcription start site. New findings related to the regulation of key vitamin D target genes in intestine and bone as well as nonclassical actions of 1,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)], including effects on breast cancer cells and on the immune system, are discussed. These studies will form the basis for future studies examining global networks regulated by the vitamin D receptor. It is becoming increasingly recognized that the actions of 1,25(OH)(2)D(3), similar to those of other steroids, is complex, involving regulation of gene activity at a range of locations.
Margolis
Ronald N
RN
Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA. margolisr@mail.nih.gov
Christakos
Sylvia
S
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D005810:Multigene Family / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014807:Vitamin D / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D014807:Vitamin D