title: Epigenetic histone modifications and master regulators as determinants of context dependent nuclear receptor activity in bone cells.
abstract: Genomic annotation of unique and combinatorial epigenetic modifications along with transcription factor occupancy is having a profound impact on our understanding of the genome. These studies have led to a better appreciation of the dynamic nature of the epigenetic and transcription factor binding components that reveal overarching principles of the genome as well as tissue specificity. In this minireview, we discuss the presence and potential functions of several of these features across the genome in osteoblast lineage cells. We examine how these features are modulated during cellular maturation, affect transcriptional output and phenotype, and how they alter the ability of cells to respond to systemic signals directed by calcemic hormones such as 1,25-dihydroxyvitamin D3 and PTH. In particular, we describe recent experiments which indicate that progressive stages of bone cell differentiation affect RUNX2 binding to the genome, modify and restrict patterns of gene expression, and dramatically alter cellular response to the vitamin D hormone. These studies expand our understanding of mechanisms that govern steroid hormone regulation of gene expression, while highlighting the increasing complexity that is evident relative to these basic cellular processes. The results also have profound implications with respect to the impact of skeletal diseases on transcriptional outcomes as well. This article is part of a Special Issue entitled Epigenetics and Bone.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, 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, WI 53706, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meyer
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Hillary C
authors.initials: HC
authors.lastname: St John
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Benkusky
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D044127:Epigenesis, Genetic; D042421:Histone Code / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D050659:Core Binding Factor Alpha 1 Subunit; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D002117:Calcitriol
keywords: Epigenetics; Genome-wide analysis; Osteoblast lineage cells; Transcription
references.citation: Nat Rev Genet. 2012 Apr 03;13(5):343-57
references.pmid: 22473383
references.citation: J Biol Chem. 2014 Jul 11;289(28):19539-54
references.pmid: 24891508
references.citation: Mol Cell. 2013 Mar 7;49(5):825-37
references.pmid: 23473601
references.citation: Nucleic Acids Res. 2011 Nov;39(21):9181-93
references.pmid: 21846776
references.citation: Annu Rev Genet. 2014;48:237-68
references.pmid: 25195505
references.citation: Mol Endocrinol. 2006 Jun;20(6):1231-47
references.pmid: 16497728
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Mol Endocrinol. 2014 Jul;28(7):1150-65
references.pmid: 24877565
references.citation: Nature. 2011 May 5;473(7345):43-9
references.pmid: 21441907
references.citation: Genome Med. 2014 Oct 28;6(10):85
references.pmid: 25473424
references.citation: J Biol Chem. 2010 May 14;285(20):15599-15610
references.pmid: 20236932
references.citation: J Mol Endocrinol. 2013 Nov 13;51(3):T37-50
references.pmid: 24130129
references.citation: Nature. 2007 May 24;447(7143):407-12
references.pmid: 17522673
references.citation: Cell Res. 2011 Apr;21(4):564-78
references.pmid: 21423274
references.citation: Mol Cell. 2013 Aug 8;51(3):310-25
references.pmid: 23932714
references.citation: Eur J Immunol. 2014 Apr;44(4):1181-93
references.pmid: 24374622
references.citation: Mol Cell. 2007 Jan 12;25(1):15-30
references.pmid: 17218268
references.citation: Curr Osteoporos Rep. 2012 Jun;10(2):151-9
references.pmid: 22544628
references.citation: Bone. 2015 Mar;72:81-91
references.pmid: 25460572
references.citation: Mol Cell Biol. 2006 Sep;26(17):6469-86
references.pmid: 16914732
references.citation: Nat Immunol. 2010 Jul;11(7):635-43
references.pmid: 20543837
references.citation: Mol Endocrinol. 2003 May;17(5):777-91
references.pmid: 12637589
references.citation: J Clin Invest. 2012 May;122(5):1803-15
references.pmid: 22523068
references.citation: Curr Osteoporos Rep. 2014 Dec;12(4):496-506
references.pmid: 25260661
references.citation: Ann N Y Acad Sci. 2008 Nov;1143:123-50
references.pmid: 19076348
references.citation: Mol Cell. 2012 Oct 12;48(1):28-38
references.pmid: 22921934
references.citation: Annu Rev Biochem. 2007;76:75-100
references.pmid: 17362198
references.citation: J Biol Chem. 2011 Jun 10;286(23):20880-91
references.pmid: 21487009
references.citation: Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):27-38
references.pmid: 22189423
references.citation: Nature. 2012 Sep 6;489(7414):91-100
references.pmid: 22955619
references.citation: J Cell Biochem. 2007 Oct 1;102(2):332-40
references.pmid: 17661352
references.citation: Nucleic Acids Res. 2013 Jan;41(2):827-41
references.pmid: 23221638
references.citation: Genome Biol. 2014 Mar 21;15(3):R52
references.pmid: 24655370
references.citation: Nat Biotechnol. 2010 Aug;28(8):817-25
references.pmid: 20657582
references.citation: Integr Biol (Camb). 2011 Apr;3(4):297-303
references.pmid: 21184003
references.citation: PLoS One. 2009;4(2):e4543
references.pmid: 19229324
references.citation: Genome Res. 2010 Oct;20(10):1352-60
references.pmid: 20736230
references.citation: J Biol Chem. 2013 Oct 4;288(40):28783-91
references.pmid: 23940046
references.citation: Bonekey Rep. 2014 Feb 05;3:499
references.pmid: 24605216
references.citation: Gene. 2013 Apr 10;518(1):171-8
references.pmid: 23235118
references.citation: Cell. 2013 Apr 25;153(3):601-13
references.pmid: 23622244
references.citation: Nature. 2010 Jan 28;463(7280):474-84
references.pmid: 20110991
references.citation: Cell. 2012 Apr 13;149(2):467-82
references.pmid: 22500808
references.citation: J Bone Miner Res. 2005 Feb;20(2):305-17
references.pmid: 15647825
references.citation: Nat Rev Genet. 2010 Jul;11(7):476-86
references.pmid: 20531367
references.citation: Mol Endocrinol. 2012 Jan;26(1):37-51
references.pmid: 22108803
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5526-34
references.pmid: 22904103
references.citation: Nat Rev Genet. 2011 Jan;12(1):7-18
references.pmid: 21116306
references.citation: Adv Exp Med Biol. 2015;827:287-310
references.pmid: 25387971
references.citation: J Biol Chem. 2008 Nov 21;283(47):32977-88
references.pmid: 18728018
references.citation: J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):136-41
references.pmid: 20171278
references.citation: Annu Rev Genomics Hum Genet. 2008;9:183-96
references.pmid: 18767962
references.citation: Bone. 2013 Jun;54(2):250-7
references.pmid: 23017659
references.citation: Mol Biol Cell. 2008 Dec;19(12):5373-86
references.pmid: 18843047
references.citation: J Biol Chem. 2014 Jun 6;289(23):16016-31
references.pmid: 24764292