title: Corepressors (NCoR and SMRT) as well as coactivators are recruited to positively regulated 1α,25-dihydroxyvitamin D3-responsive genes.
abstract: Transcription factors require coactivators and corepressors to modulate transcription in mammalian cells. The vitamin D receptor (VDR) utilizes coactivators and corepressors to gain tight control over the activity of a diverse set of genes that can regulate calcium transport, slow proliferation and promote immune responses. We have recently established the VDR/RXR cistrome in human colon cancer cells and have linked these binding sites to the genes that are regulated by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In additional studies described herein, we demonstrate that the coactivators SRC1, CBP and MED1 are recruited to upregulated genes to facilitate transcription as expected. SRC1 was the most highly correlated to VDR/RXR binding (50%). However, we also found that corepressor molecules such as NCoR and SMRT were present along with SRC1, CBP or MED1 at these 1,25(OH)2D3 activated gene enhancers. Interestingly, genome-wide NCoR binding mimicked VDR binding by increasing its association with VDR binding in response to 1,25(OH)2D3 treatment. Overall, these data indicate a complex role for corepressor and coactivator complexes in the activation or active repression of 1,25(OH)2D3 responsive genes. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meyer
authors.forename: J Wesley
authors.initials: JW
authors.lastname: Pike
mesh_terms: D050882:CREB-Binding Protein / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D056913:Mediator Complex Subunit 1 / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; C579457:VDR protein, human; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D002117:Calcitriol