title: Genomic Determinants of Vitamin D-Regulated Gene Expression.
abstract: Insight into mechanisms that link the actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to the regulation of gene expression has evolved extensively since the initial discovery of a nuclear protein known as the vitamin D receptor (VDR). Perhaps most important was the molecular cloning of this receptor which enabled its inclusion within the nuclear receptor gene family and further studies of both its structure and regulatory function. Current studies are now refocused on the vitamin D hormone's action at the genome, where VDR together with other transcription factors coordinates the recruitment of chromatin active coregulatory complexes that participate directly in the modification of gene output. These studies highlight the role of chromatin in the expression of genes and the dynamic impact of the epigenetic landscape that contextualizes individual gene loci thus influencing the VDR's transcriptional actions. In this chapter, we summarize advances made over the past few years in understanding vitamin D action on a genome-wide scale, focusing on overarching principles that have emerged at this level. Of particular significance is the finding that dynamic changes that occur to the genome during cellular differentiation at both genetic and epigenetic levels profoundly alter the ability of 1,25(OH)2D3 and its receptor to regulate gene expression. We address the broad impact of differentiation on specific epigenetic histone modifications that occur across the genome and the ability of the VDR to influence this activity at selected gene loci as well. These studies advance our understanding of not only vitamin D action but also of the complex and dynamic role played by the genome itself as a major determinant of VDR activity.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: pike@biochem.wisc.edu.
authors.forename: J Wesley
authors.initials: JW
authors.lastname: Pike
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meyer
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Benkusky
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: St John
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Carlson
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Melda
authors.initials: M
authors.lastname: Onal
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Sohel
authors.initials: S
authors.lastname: Shamsuzzaman
mesh_terms: D002117:Calcitriol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D023281:Genomics; D006801:Humans; D010006:Osteoblasts / Q000502:physiology; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D002117:Calcitriol
keywords: Distal gene regulation; Genome-wide ChIP-seq analysis; Histone epigenetic modification; Ligand-independent DNA binding; Osteoblast-lineage cells; Transcription
references.citation: J Clin Endocrinol Metab. 1978 Dec;47(6):1303-10
references.pmid: 233695
references.citation: Nature. 2012 Sep 6;489(7414):91-100
references.pmid: 22955619
references.citation: Proc Natl Acad Sci U S A. 1988 May;85(10):3294-8
references.pmid: 2835767
references.citation: Science. 1988 May 13;240(4854):889-95
references.pmid: 3283939
references.citation: J Bone Miner Res. 2005 Feb;20(2):305-17
references.pmid: 15647825
references.citation: Annu Rev Biochem. 2007;76:75-100
references.pmid: 17362198
references.citation: J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):344-6
references.pmid: 17223342
references.citation: Mol Endocrinol. 2006 Jun;20(6):1231-47
references.pmid: 16497728
references.citation: Mol Cell. 2013 Mar 7;49(5):825-37
references.pmid: 23473601
references.citation: Proc Natl Acad Sci U S A. 1982 Dec;79(24):7719-23
references.pmid: 6296847
references.citation: J Biol Chem. 2010 May 14;285(20):15599-610
references.pmid: 20236932
references.citation: Bonekey Rep. 2014 Jan 08;3:482
references.pmid: 24466413
references.citation: Cell. 2013 Apr 25;153(3):601-13
references.pmid: 23622244
references.citation: N Engl J Med. 1981 Jun 25;304(26):1588-91
references.pmid: 6262646
references.citation: J Cell Biochem. 2015 Feb;116(2):320-30
references.pmid: 25211367
references.citation: J Biol Chem. 1995 Jan 27;270(4):1675-8
references.pmid: 7829502
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9428-33
references.pmid: 17517646
references.citation: J Pediatr Endocrinol Metab. 2010 Aug;23 (8):843-50
references.pmid: 21073129
references.citation: Science. 1984 May 25;224(4651):879-81
references.pmid: 6326262
references.citation: Proc Natl Acad Sci U S A. 1989 Jun;86(12):4455-9
references.pmid: 2786632
references.citation: Nat Genet. 1997 Aug;16(4):391-6
references.pmid: 9241280
references.citation: J Biol Chem. 2014 Jul 11;289(28):19539-54
references.pmid: 24891508
references.citation: J Biol Chem. 2014 Jun 6;289(23):16016-31
references.pmid: 24764292
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9831-5
references.pmid: 9275211
references.citation: Mol Cell Endocrinol. 1990 Sep 10;72(3):C57-62
references.pmid: 1963156
references.citation: Proc Natl Acad Sci U S A. 1979 Nov;76(11):5485-9
references.pmid: 230478
references.citation: Biochemistry. 1986 Aug 12;25(16):4523-34
references.pmid: 2429689
references.citation: J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:5-11
references.pmid: 24239506
references.citation: Nature. 2007 May 24;447(7143):407-12
references.pmid: 17522673
references.citation: Genome Res. 2010 Oct;20(10):1352-60
references.pmid: 20736230
references.citation: J Biol Chem. 2011 Jun 10;286(23):20880-91
references.pmid: 21487009
references.citation: Cell. 2014 Sep 25;159(1):80-93
references.pmid: 25259922
references.citation: Science. 1988 Dec 23;242(4886):1702-5
references.pmid: 2849209
references.citation: Mol Genet Metab. 2014 Jan;111(1):33-40
references.pmid: 24246681
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Nucleic Acids Res. 2011 Nov;39(21):9181-93
references.pmid: 21846776
references.citation: J Biol Chem. 1990 Dec 15;265(35):21881-8
references.pmid: 2174889
references.citation: J Cell Biochem. 2004 Jun 1;92(3):436-44
references.pmid: 15156556
references.citation: Endocrinology. 2001 Dec;142(12):5386-9
references.pmid: 11713240
references.citation: Proc Natl Acad Sci U S A. 1989 Feb;86(4):1143-7
references.pmid: 2784002
references.citation: J Biol Chem. 2015 Apr 24;290(17):11093-107
references.pmid: 25773540
references.citation: Mol Endocrinol. 2010 Jan;24(1):128-47
references.pmid: 19897601
references.citation: J Biol Chem. 2015 Jul 17;290(29):18199-215
references.pmid: 26041780
references.citation: Mol Endocrinol. 2009 Dec;23(12):2095-110
references.pmid: 19880655
references.citation: Bone. 2015 Mar;72:81-91
references.pmid: 25460572
references.citation: Endocr Rev. 1999 Apr;20(2):156-88
references.pmid: 10204116
references.citation: Rev Endocr Metab Disord. 2012 Mar;13(1):3-19
references.pmid: 21845365
references.citation: J Biol Chem. 1974 Feb 25;249(4):1251-7
references.pmid: 4360685
references.citation: J Biol Chem. 2008 Nov 21;283(47):32977-88
references.pmid: 18728018
references.citation: J Biol Chem. 1974 Feb 25;249(4):1258-62
references.pmid: 4360686
references.citation: J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):136-41
references.pmid: 20171278
references.citation: J Steroid Biochem Mol Biol. 2013 Jul;136:120-4
references.pmid: 22944139
references.citation: Endocrinology. 2014 Nov;155(11):4137-48
references.pmid: 25147982
references.citation: Mol Cell. 2007 Jan 12;25(1):15-30
references.pmid: 17218268
references.citation: J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):130-5
references.pmid: 20214983
references.citation: N Engl J Med. 1978 May 4;298(18):996-9
references.pmid: 205789
references.citation: Science. 1987 Mar 6;235(4793):1214-7
references.pmid: 3029866
references.citation: Mol Endocrinol. 2007 Jan;21(1):197-214
references.pmid: 17053039
references.citation: Mol Endocrinol. 2012 Jan;26(1):37-51
references.pmid: 22108803
references.citation: J Steroid Biochem. 1988;30(1-6):41-6
references.pmid: 2838696
references.citation: Endocrinology. 2008 Jan;149(1):146-53
references.pmid: 17932217
references.citation: Proc Natl Acad Sci U S A. 1969 Jan;62(1):155-62
references.pmid: 5253652
references.citation: J Bone Miner Res. 2015 May;30(5):855-68
references.pmid: 25431114
references.citation: Science. 2013 Feb 15;339(6121):819-23
references.pmid: 23287718
references.citation: Mol Endocrinol. 2003 May;17 (5):777-91
references.pmid: 12637589
references.citation: Mol Endocrinol. 1989 Apr;3(4):635-44
references.pmid: 2542779
references.citation: Annu Rev Nutr. 1991;11:189-216
references.pmid: 1654066
references.citation: Mol Endocrinol. 2005 Apr;19(4):855-62
references.pmid: 15591533
references.citation: Mol Cell Biol. 2006 Sep;26(17):6469-86
references.pmid: 16914732
references.citation: Endocrinology. 2014 Jun;155(6):2064-76
references.pmid: 24693968
references.citation: J Biol Chem. 1994 Apr 8;269(14 ):10545-50
references.pmid: 8144641
references.citation: Endocr Rev. 2008 Oct;29(6):726-76
references.pmid: 18694980
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98 (13):7498-503
references.pmid: 11416220
references.citation: Proc Natl Acad Sci U S A. 1988 Feb;85(4):1005-9
references.pmid: 2829212
references.citation: Blood. 2005 Aug 15;106(4):1232-9
references.pmid: 15845900
references.citation: Mol Endocrinol. 2014 Jul;28(7):1150-65
references.pmid: 24877565