Specific histone lysine 4 methylation patterns define TR-binding capacity and differentiate direct T3 responses.
The diversity of thyroid hormone T(3) effects in vivo makes their molecular analysis particularly challenging. Indeed, the current model of the action of T(3) and its receptors on transcription does not reflect this diversity. Here, T(3)-dependent amphibian metamorphosis was exploited to investigate, in an in vivo developmental context, how T(3) directly regulates gene expression. Two, direct positively regulated T(3)-response genes encoding transcription factors were analyzed: thyroid hormone receptor β (TRβ) and TH/bZIP. Reverse transcription-real-time quantitative PCR analysis on Xenopus tropicalis tadpole brain and tail fin showed differences in expression levels in premetamorphic tadpoles (lower for TH/bZIP than for TRβ) and differences in induction after T(3) treatment (lower for TRβ than for TH/bZIP). To dissect the mechanisms underlying these differences, chromatin immunoprecipitation was used. T(3) differentially induced RNA polymerase II and histone tail acetylation as a function of transcriptional level. Gene-specific patterns of TR binding were found on the different T(3) -responsive elements (higher for TRβ than for TH/bZIP), correlated with gene-specific modifications of H3K4 methylation (higher for TRβ than for TH/bZIP). Moreover, tissue-specific modifications of H3K27 were found (lower in brain than in tail fin). This first in vivo analysis of the association of histone modifications and TR binding/gene activation during vertebrate development for any nuclear receptor indicate that chromatin context of thyroid-responsive elements loci controls the capacity to bind TR through variations in histone H3K4 methylation, and that the histone code, notably H3, contributes to the fine tuning of gene expression that underlies complex physiological T(3) responses.
Muséum National d’Histoire Naturelle, Départment Régulation Développement et Diversité Moléculaire, Unité Mixte de Recherche 7221 Centre National de la Recherche Scientifique, Evolution des régulations endocriniennes, 75231 Paris cedex 05, France.
Patrice
P
Bilesimo
Pascale
P
Jolivet
Gladys
G
Alfama
Nicolas
N
Buisine
Sebastien
S
Le Mevel
Emmanuelle
E
Havis
Barbara A
BA
Demeneix
Laurent M
LM
Sachs
D000107:Acetylation; D000818:Animals; D030801:Animals, Genetically Modified; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics; D008745:Methylation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism*; D014981:Xenopus
D050976:Basic-Leucine Zipper Transcription Factors; D006657:Histones; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D012319:RNA Polymerase II
Mol Cell. 2007 Jan 12;25(1):15-30
17218268
J Biol Chem. 2005 May 6;280(18):17732-6
15760899
EMBO J. 2003 May 1;22(9):2146-55
12727881
Mol Endocrinol. 1999 Dec;13(12):2076-89
10598583
Nature. 2009 May 7;459(7243):108-12
19295514
Endocrinology. 2008 Nov;149(11):5610-8
18635662
Cell. 2007 Oct 5;131(1):29-32
17923085
J Biol Chem. 2006 Nov 17;281(46):35289-95
16987819
EMBO J. 2006 Oct 18;25(20):4943-51
17006540
Cancer Res. 2004 Aug 1;64(15):5245-50
15289330
J Biol Chem. 2005 Dec 16;280(50):41222-8
16236718
Dev Cell. 2009 Sep;17(3):425-34
19758566
Development. 1996 Oct;122(10):3173-83
8898230
EMBO J. 2003 Jul 1;22(13):3403-10
12840002
Cell. 2004 Dec 29;119(7):941-53
15620353
Cell. 1995 Dec 15;83(6):835-9
8521507
Science. 2002 Nov 1;298(5595):1039-43
12351676
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13138-43
11078533
J Biol Chem. 1994 Oct 7;269(40):24699-705
7929143
Int J Mol Med. 2001 Dec;8(6):595-601
11712071
Int J Dev Biol. 2009;53(2-3):335-54
19412890
Nature. 2005 Sep 15;437(7057):436-9
16079795
Genome Res. 2008 Aug;18(8):1314-24
18562678
Cell. 2006 Apr 21;125(2):315-26
16630819
Dev Cell. 2008 May;14(5):798-809
18477461
J Biol Chem. 2009 Dec 4;284(49):34167-78
19801647
Cell. 2007 Jul 13;130(1):77-88
17632057
Nat Genet. 2010 Apr;42(4):343-7
20208536
Cell. 2007 Feb 9;128(3):505-518
17289570
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7322-6
8346251
EMBO Rep. 2003 Sep;4(9):883-8
12947412
EMBO Rep. 2006 Oct;7(10):1035-9
16936638
Mol Cell Biol. 2007 Apr;27(7):2746-57
17242185
Nature. 1997 May 1;387(6628):16-7
9139815
EMBO J. 2009 Jun 17;28(12):1697-707
19407817
Dev Biol. 2007 Jun 1;306(1):20-33
17449026
J Mol Biol. 2007 Sep 14;372(2):298-316
17663992
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7869-74
11427732
Nature. 2000 Jan 6;403(6765):41-5
10638745
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10739-44
11517345
EMBO Rep. 2005 May;6(5):445-51
15832170
Genes Dev. 2008 May 1;22(9):1115-40
18451103
Mol Cell Biol. 2005 Jan;25(1):324-35
15601853
Nat Cell Biol. 2007 Dec;9(12):1428-35
18037880
Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
16261189