title: Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells.
abstract: TRα1 and TRβ1, the two main thyroid hormone receptors in mammals, are transcription factors that share similar properties. However, their respective functions are very different. This functional divergence might be explained in two ways: it can reflect different expression patterns or result from different intrinsic properties of the receptors. We tested this second hypothesis by comparing the repertoires of 3,3',5-triiodo-L-thyronine (T3)-responsive genes of two neural cell lines, expressing either TRα1 or TRβ1. Using transcriptome analysis, we found that a substantial fraction of the T3 target genes display a marked preference for one of the two receptors. So when placed alone in identical situations, the two receptors have different repertoires of target genes. Chromatin occupancy analysis, performed at a genome-wide scale, revealed that TRα1 and TRβ1 cistromes were also different. However, receptor-selective regulation of T3 target genes did not result from receptor-selective chromatin occupancy of their promoter regions. We conclude that modification of TRα1 and TRβ1 intrinsic properties contributes in a large part to the divergent evolution of the receptors' function, at least during neurodevelopment.
authors: Université de Lyon, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique, École Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
authors: Fabrice
authors: F
authors: Chatonnet
authors: Romain
authors: R
authors: Guyot
authors: Gérard
authors: G
authors: Benoît
authors: Frederic
authors: F
authors: Flamant
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D016678:Genome; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D059467:Transcriptome
chemical_list: D002843:Chromatin; D011988:Receptors, Thyroid Hormone
references: Nat Rev Drug Discov. 2009 Apr;8(4):308-20
references: 19337272
references: J Dev Behav Pediatr. 1995 Dec;16(6):406-11
references: 8746549
references: Nat Methods. 2006 Dec;3(12):1013-9
references: 17060908
references: Nat Rev Mol Cell Biol. 2005 Jul;6(7):542-54
references: 15957004
references: Toxicology. 2011 Apr 28;283(1):41-8
references: 21315791
references: Dev Biol. 2009 Feb 1;326(1):155-68
references: 19056375
references: Pharmacol Rev. 2006 Dec;58(4):705-11
references: 17132849
references: J Mol Biol. 2006 Jul 14;360(3):586-98
references: 16781732
references: Environ Toxicol Pharmacol. 2007 May;23(3):302-7
references: 21783772
references: Cell. 1992 Jan 10;68(1):33-51
references: 1732063
references: Mol Endocrinol. 2012 Jun;26(6):926-39
references: 22570333
references: Nature. 2012 Apr 11;484(7393):251-5
references: 22498630
references: Mol Endocrinol. 2007 Oct;21(10):2350-60
references: 17622582
references: N Engl J Med. 1997 Sep 25;337(13):888-96
references: 9302303
references: Mol Cell Biol. 2007 Apr;27(7):2442-51
references: 17261597
references: Endocrinology. 2012 Jan;153(1):501-11
references: 22067320
references: Mol Cell Neurosci. 2010 May;44(1):68-77
references: 20193766
references: J Biol Chem. 2001 Sep 7;276(36):34227-34
references: 11454868
references: Genes Dev. 1999 May 15;13(10):1329-41
references: 10346821
references: Biochim Biophys Acta. 2013 Jul;1830(7):3900-7
references: 22704954
references: Development. 2012 Mar;139(6):1045-57
references: 22354838
references: EMBO J. 2003 Apr 1;22(7):1579-87
references: 12660164
references: Pharmacol Ther. 2011 Jul;131(1):33-9
references: 21504761
references: J Neurosci. 1996 Dec 15;16(24):7832-40
references: 8987811
references: EMBO J. 1993 Dec 15;12(13):5029-41
references: 8262045
references: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):439-43
references: 8290545
references: Thyroid. 2000 Jan;10(1):41-52
references: 10691312
references: Toxicol Sci. 2011 Dec;124(2):432-45
references: 21964421
references: Genes Dev. 2005 Sep 15;19(18):2152-63
references: 16131613
references: Mol Endocrinol. 2009 Nov;23(11):1758-75
references: 19628582
references: Clin Exp Pharmacol Physiol Suppl. 1998 Nov;25:S2-11
references: 9809185
references: J Cereb Blood Flow Metab. 2010 Feb;30(2):323-35
references: 19861975
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9913-8
references: 11481455
references: EMBO J. 2011 Oct 14;30(23):4764-76
references: 22002538
references: Genes Dev. 1998 Nov 1;12(21):3343-56
references: 9808622
references: J Biol Chem. 2007 Apr 27;282(17):12458-66
references: 17311926
references: J Invest Dermatol. 2005 May;124(5):1034-43
references: 15854046
references: J Biol Chem. 2004 Dec 17;279(51):53562-70
references: 15466858
references: J Cell Sci. 2006 Jul 15;119(Pt 14):2975-84
references: 16803873
references: Nature. 1995 May 18;375(6528):203-11
references: 7746322
references: J Biol Chem. 2002 Nov 15;277(46):44455-61
references: 12200415
references: J Cell Biochem. 2009 May 1;107(1):30-9
references: 19247990
references: Endocrinology. 2011 Apr;152(4):1713-21
references: 21303950
references: Mol Cell Biol. 2001 Jul;21(14):4748-60
references: 11416150
references: Rev Endocr Metab Disord. 2000 Jan;1(1-2):97-108
references: 11704998
references: Dev Biol. 2011 Aug 15;356(2):350-8
references: 21621530
references: Nat Cell Biol. 2009 Jun;11(6):747-52
references: 19448625
references: Mol Cell Endocrinol. 1994 Apr;100(1-2):125-31
references: 8056146
references: Neuron. 2011 Jun 9;70(5):966-78
references: 21658588
references: Mol Endocrinol. 2010 Oct;24(10):1904-16
references: 20739404
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Biostatistics. 2007 Apr;8(2):414-32
references: 16928955
references: N Engl J Med. 2012 Jan 19;366(3):243-9
references: 22168587
references: PLoS One. 2012;7(5):e30703
references: 22586439
references: N Engl J Med. 2012 Apr 12;366(15):1451-3
references: 22494134
references: Curr Biol. 2011 Sep 27;21(18):R726-37
references: 21959163
references: Mol Endocrinol. 1991 Sep;5(9):1339-50
references: 1663215