Multiple mechanisms regulate H3 acetylation of enhancers in response to thyroid hormone


Autoři: Stine M. Præstholm aff001;  Majken S. Siersbæk aff001;  Ronni Nielsen aff001;  Xuguang Zhu aff002;  Anthony Hollenberg aff003;  Sheue-yann Cheng aff002;  Lars Grøntved aff001;  Anthony N. Hollenberg aff003
Působiště autorů: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark aff001;  Laboratory of Molecular Biology, CCR, NCI, NIH, Bethesda, Maryland, United States of America aff002;  Division of Endocrinology, Diabetes and Metabolism Weill Cornell Medicine, New York, New York, United States of America aff003
Vyšlo v časopise: Multiple mechanisms regulate H3 acetylation of enhancers in response to thyroid hormone. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008770
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008770

Souhrn

Hormone-dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is mostly explained by a bimodal switch model, where histone deacetylases (HDACs) disassociate from chromatin, and histone acetyl transferases (HATs) are recruited. This model builds on decades of research on steroid receptor regulation of transcription. Yet, the general concept of the bimodal switch model has not been rigorously tested genome wide. We have used a genomics approach to study enhancer hyperacetylation by the thyroid hormone receptor (TR), described to operate as a bimodal switch. H3 acetylation, HAT and HDAC ChIP-seq analyses of livers from hypo- and hyperthyroid wildtype, TR deficient and NCOR1 disrupted mice reveal three types of thyroid hormone (T3)-regulated enhancers. One subset of enhancers is bound by HDAC3-NCOR1 in the absence of hormone and constitutively occupy TR and HATs irrespective of T3 levels, suggesting a poised enhancer state in absence of hormone. In presence of T3, HDAC3-NCOR1 dissociates from these enhancers leading to histone hyperacetylation, suggesting a histone acetylation rheostat function of HDACs at poised enhancers. Another subset of enhancers, not occupied by HDACs, is hyperacetylated in a T3-dependent manner, where TR is recruited to chromatin together with HATs. Lastly, a subset of enhancers, is not occupied directly by TR yet requires TR for histone hyperacetylation. This indirect enhancer activation involves co-association with TR bound enhancers within super-enhancers or topological associated domains. Collectively, this demonstrates various mechanisms controlling hormone-dependent transcription and adds significant details to the otherwise simple bimodal switch model.

Klíčová slova:

Gene expression – Gene regulation – Histones – Chromatin – Mammalian genomics – Mouse models – Thyroid hormones – Histone acetylation


Zdroje

1. Heinz S, Romanoski CE, Benner C, Glass CK (2015) The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol 16: 144–154. doi: 10.1038/nrm3949 25650801

2. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, et al. (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107: 21931–21936. doi: 10.1073/pnas.1016071107 21106759

3. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, et al. (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459: 108–112. doi: 10.1038/nature07829 19295514

4. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, et al. (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38: 576–589. doi: 10.1016/j.molcel.2010.05.004 20513432

5. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, et al. (2011) A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470: 279–283. doi: 10.1038/nature09692 21160473

6. Millard CJ, Watson PJ, Fairall L, Schwabe JWR (2013) An evolving understanding of nuclear receptor coregulator proteins. J Mol Endocrinol 51: T23–36. doi: 10.1530/JME-13-0227 24203923

7. Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J 15: 3667–3675.

8. Jeyakumar M, Tanen MR, Bagchi MK (1997) Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor. Mol Endocrinol 11: 755–767. doi: 10.1210/mend.11.6.0003 9171239

9. Oñate SA, Tsai SY, Tsai MJ, O’Malley BW (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270: 1354–1357.

10. Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, et al. (1996) Role of CBP/P300 in nuclear receptor signalling. Nature 383: 99–103. doi: 10.1038/383099a0 8779723

11. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, et al. (1996) A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85: 403–414. doi: 10.1016/s0092-8674(00)81118-6

12. Fondell JD, Ge H, Roeder RG (1996) Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci U S A 93: 8329–8333.

13. Chen JD, Evans RM (1995) A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 377: 454–457. doi: 10.1038/377454a0 7566127

14. Hörlein AJ, Näär AM, Heinzel T, Torchia J, Gloss B, et al. (1995) Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377: 397–404. doi: 10.1038/377397a0 7566114

15. Ishizuka T, Lazar MA (2003) The N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptor. Mol Cell Biol 23: 5122–5131. doi: 10.1128/MCB.23.15.5122–5131.2003

16. Oberoi J, Fairall L, Watson PJ, Yang J-C, Czimmerer Z, et al. (2011) Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. Nat Struct Mol Biol 18: 177–184. doi: 10.1038/nsmb.1983 21240272

17. Yoon H-G, Chan DW, Huang Z-Q, Li J, Fondell JD, et al. (2003) Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1. EMBO J 22: 1336–1346. doi: 10.1093/emboj/cdg120 12628926

18. Guenther MG, Lane WS, Fischle W, Verdin E, Lazar MA, et al. (2000) A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness. Genes Dev 14: 1048–1057.

19. Zhang J, Kalkum M, Chait BT, Roeder RG (2002) The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2. Mol Cell 9: 611–623. doi: 10.1016/S1097-2765(02)00468-9

20. Cohen RN, Wondisford FE, Hollenberg AN (1998) Two separate NCoR (nuclear receptor corepressor) interaction domains mediate corepressor action on thyroid hormone response elements. Mol Endocrinol 12: 1567–1581. doi: 10.1210/mend.12.10.0188 9773980

21. Seol W, Mahon MJ, Lee YK, Moore DD (1996) Two receptor interacting domains in the nuclear hormone receptor corepressor RIP13/N-CoR. Mol Endocrinol 10: 1646–1655. doi: 10.1210/mend.10.12.8961273 8961273

22. Hu X, Lazar MA (1999) The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors. Nature 402: 93–96. doi: 10.1038/47069 10573424

23. McInerney EM, Rose DW, Flynn SE, Westin S, Mullen TM, et al. (1998) Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation. Genes Dev 12: 3357–3368. doi: 10.1101/gad.12.21.3357 9808623

24. Wagner RL, Apriletti JW, McGrath ME, West BL, Baxter JD, et al. (1995) A structural role for hormone in the thyroid hormone receptor. Nature 378: 690–697. doi: 10.1038/378690a0 7501015

25. Feng W, Ribeiro RC, Wagner RL, Nguyen H, Apriletti JW, et al. (1998) Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors. Science 280: 1747–1749.

26. Lin BC, Hong SH, Krig S, Yoh SM, Privalsky ML (1997) A conformational switch in nuclear hormone receptors is involved in coupling hormone binding to corepressor release. Mol Cell Biol 17: 6131–6138.

27. Liu Y, Xia X, Fondell JD, Yen PM (2006) Thyroid hormone-regulated target genes have distinct patterns of coactivator recruitment and histone acetylation. Mol Endocrinol 20: 483–490. doi: 10.1210/me.2005-0101 16254015

28. Lee KC, Li J, Cole PA, Wong J, Kraus WL (2003) Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivators. Mol Endocrinol 17: 908–922. doi: 10.1210/me.2002-0308 12586842

29. Singh BK, Sinha RA, Ohba K, Yen PM (2017) Role of thyroid hormone in hepatic gene regulation, chromatin remodeling, and autophagy. Mol Cell Endocrinol 458: 160–168. doi: 10.1016/j.mce.2017.02.018 28216439

30. Perissi V, Rosenfeld MG (2005) Controlling nuclear receptors: the circular logic of cofactor cycles. Nat Rev Mol Cell Biol 6: 542–554. doi: 10.1038/nrm1680 15957004

31. Flamant F, Cheng S-Y, Hollenberg AN, Moeller LC, Samarut J, et al. (2017) Thyroid hormone signaling pathways: time for a more precise nomenclature. Endocrinology 158: 2052–2057. doi: 10.1210/en.2017-00250 28472304

32. Grøntved L, Waterfall JJ, Kim DW, Baek S, Sung M-H, et al. (2015) Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling. Nat Commun 6: 7048. doi: 10.1038/ncomms8048 25916672

33. Ramadoss P, Abraham BJ, Tsai L, Zhou Y, Costa-e-Sousa RH, et al. (2014) Novel mechanism of positive versus negative regulation by thyroid hormone receptor β1 (TRβ1) identified by genome-wide profiling of binding sites in mouse liver. J Biol Chem 289: 1313–1328. doi: 10.1074/jbc.M113.521450 24288132

34. Barnes CE, English DM, Cowley SM (2019) Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription. Essays Biochem 63: 97–107. doi: 10.1042/EBC20180061 30940741

35. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, et al. (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40: 897–903. doi: 10.1038/ng.154 18552846

36. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43–49. doi: 10.1038/nature09906 21441907

37. Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, et al. (2014) A comparative encyclopedia of DNA elements in the mouse genome. Nature 515: 355–364. doi: 10.1038/nature13992 25409824

38. Mendoza A, Astapova I, Shimizu H, Gallop MR, Al-Sowaimel L, et al. (2017) NCoR1-independent mechanism plays a role in the action of the unliganded thyroid hormone receptor. Proc Natl Acad Sci U S A 114. doi: 10.1073/pnas.1706917114 28923959

39. Kaneshige M, Kaneshige K, Zhu X, Dace A, Garrett L, et al. (2000) Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Proc Natl Acad Sci U S A 97: 13209–13214. doi: 10.1073/pnas.230285997 11069286

40. Parrilla R, Mixson AJ, McPherson JA, McClaskey JH, Weintraub BD (1991) Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two “hot spot” regions of the ligand binding domain. J Clin Invest 88: 2123–2130. doi: 10.1172/JCI115542 1661299

41. Hiroi Y, Kim H-H, Ying H, Furuya F, Huang Z, et al. (2006) Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci U S A 103: 14104–14109. doi: 10.1073/pnas.0601600103 16966610

42. Madsen JGS, Rauch A, Van Hauwaert EL, Schmidt SF, Winnefeld M, et al. (2018) Integrated analysis of motif activity and gene expression changes of transcription factors. Genome Res 28: 243–255. doi: 10.1101/gr.227231.117 29233921

43. Yu M, Ren B (2017) The Three-Dimensional Organization of Mammalian Genomes. Annu Rev Cell Dev Biol 33: 265–289. doi: 10.1146/annurev-cellbio-100616-060531 28783961

44. Schmitt AD, Hu M, Jung I, Xu Z, Qiu Y, et al. (2016) A compendium of chromatin contact maps reveals spatially active regions in the human genome. Cell Rep 17: 2042–2059. doi: 10.1016/j.celrep.2016.10.061 27851967

45. Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, et al. (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159: 1665–1680. doi: 10.1016/j.cell.2014.11.021 25497547

46. Kim YH, Marhon SA, Zhang Y, Steger DJ, Won K-J, et al. (2018) Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription. Science 359: 1274–1277. doi: 10.1126/science.aao6891 29439026

47. Holmqvist P-H, Boija A, Philip P, Crona F, Stenberg P, et al. (2012) Preferential genome targeting of the CBP co-activator by Rel and Smad proteins in early Drosophila melanogaster embryos. PLoS Genet 8: e1002769. doi: 10.1371/journal.pgen.1002769 22737084

48. Ito M, Yuan CX, Okano HJ, Darnell RB, Roeder RG (2000) Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. Mol Cell 5: 683–693. doi: 10.1016/S1097-2765(00)80247-6

49. Sharma D, Fondell JD (2002) Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci U S A 99: 7934–7939. doi: 10.1073/pnas.122004799 12034878

50. Astapova I, Lee LJ, Morales C, Tauber S, Bilban M, et al. (2008) The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo. Proc Natl Acad Sci U S A 105: 19544–19549. doi: 10.1073/pnas.0804604105 19052228

51. Schübeler D, MacAlpine DM, Scalzo D, Wirbelauer C, Kooperberg C, et al. (2004) The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev 18: 1263–1271. doi: 10.1101/gad.1198204 15175259

52. Castillo AI, Sánchez-Martínez R, Moreno JL, Martínez-Iglesias OA, Palacios D, et al. (2004) A permissive retinoid X receptor/thyroid hormone receptor heterodimer allows stimulation of prolactin gene transcription by thyroid hormone and 9-cis-retinoic acid. Mol Cell Biol 24: 502–513.

53. Li D, Li T, Wang F, Tian H, Samuels HH (2002) Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer. Mol Cell Biol 22: 5782–5792.

54. Li J, O’Malley BW, Wong J (2000) p300 requires its histone acetyltransferase activity and SRC-1 interaction domain to facilitate thyroid hormone receptor activation in chromatin. Mol Cell Biol 20: 2031–2042.

55. Mathur M, Tucker PW, Samuels HH (2001) PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Mol Cell Biol 21: 2298–2311. doi: 10.1128/MCB.21.7.2298–2311.2001

56. Heinzel T, Lavinsky RM, Mullen TM, Söderstrom M, Laherty CD, et al. (1997) A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387: 43–48. doi: 10.1038/387043a0 9139820

57. Bose DA, Donahue G, Reinberg D, Shiekhattar R, Bonasio R, et al. (2017) RNA binding to CBP stimulates histone acetylation and transcription. Cell 168: 135–149.e22. doi: 10.1016/j.cell.2016.12.020 28086087

58. Ait-Si-Ali S, Ramirez S, Barre FX, Dkhissi F, Magnaghi-Jaulin L, et al. (1998) Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A. Nature 396: 184–186. doi: 10.1038/24190 9823900

59. Huang W-C, Chen C-C (2005) Akt phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity. Mol Cell Biol 25: 6592–6602. doi: 10.1128/MCB.25.15.6592–6602.2005

60. Perissi V, Dasen JS, Kurokawa R, Wang Z, Korzus E, et al. (1999) Factor-specific modulation of CREB-binding protein acetyltransferase activity. Proc Natl Acad Sci U S A 96: 3652–3657.

61. Yen PM, Feng X, Flamant F, Chen Y, Walker RL, et al. (2003) Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice. EMBO Rep 4: 581–587. doi: 10.1038/sj.embor.embor862 12776178

62. Hönes GS, Rakov H, Logan J, Liao X-H, Werbenko E, et al. (2017) Noncanonical thyroid hormone signaling mediates cardiometabolic effects in vivo. Proc Natl Acad Sci U S A 114: E11323–E11332. doi: 10.1073/pnas.1706801115 29229863

63. Huang J, Li K, Cai W, Liu X, Zhang Y, et al. (2018) Dissecting super-enhancer hierarchy based on chromatin interactions. Nat Commun 9: 943. doi: 10.1038/s41467-018-03279-9 29507293

64. Fozzatti L, Kim DW, Park JW, Willingham MC, Hollenberg AN, et al. (2013) Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor α. Proc Natl Acad Sci U S A 110: 7850–7855. doi: 10.1073/pnas.1222334110 23610395

65. Park S, Han CR, Park JW, Zhao L, Zhu X, et al. (2017) Defective erythropoiesis caused by mutations of the thyroid hormone receptor α gene. PLoS Genet 13: e1006991. doi: 10.1371/journal.pgen.1006991 28910278

66. Siersbæk M, Varticovski L, Yang S, Baek S, Nielsen R, et al. (2017) High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss. Sci Rep 7: 40220. doi: 10.1038/srep40220 28071704

67. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, et al. (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29: 15–21. doi: 10.1093/bioinformatics/bts635 23104886

68. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15: 550. doi: 10.1186/s13059-014-0550-8 25516281

69. Saeed AI, Sharov V, White J, Li J, Liang W, et al. (2003) TM4: a free, open-source system for microarray data management and analysis. BioTechniques 34: 374–378. doi: 10.2144/03342mt01 12613259

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2020 Číslo 5

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Kurz originály vs. generika
nový kurz
Autoři:

Klinická farmakokinetika betablokátorů
Autoři:

Současné možnosti terapie osteoartrózy
Autoři: MUDr. Jakub Holešovský

Preferovaná úlevová léčba Asthma Bronchiale
Autoři: PharmDr. Petr Sedlák

Inhibitory karboanhydrázy v léčbě glaukomu
Autoři: MUDr. Petr Výborný, CSc., FEBO

Všechny kurzy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se