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Protoplasma

, Volume 254, Issue 3, pp 1175–1185 | Cite as

Genomic effects of glucocorticoids

  • Ivana Grbesa
  • Ofir HakimEmail author
Review Article

Abstract

Glucocorticoids and their receptor (GR) have been an important area of research because of their pleiotropic physiological functions and extensive use in the clinic. In addition, the association between GR and glucocorticoids, which is highly specific, leads to rapid nuclear translocation where GR associates with chromatin to regulate gene transcription. This simplified model system has been instrumental for studying the complexity of transcription regulation processes occurring at chromatin. In this review we discuss our current understanding of GR action that has been enhanced by recent developments in genome wide measurements of chromatin accessibility, histone marks, chromatin remodeling and 3D chromatin structure in various cell types responding to glucocorticoids.

Keywords

ChIP-seq Chromatin Chromatin accessibility Enhancers Glucocorticoid receptor Glucocorticoids Long-range interactions Transcription Transcription factor 

Abbreviations

AP-1

Activator protein 1

ChIP

Chromatin immunoprecipitation

ChIP-exo

ChIP combined with lambda exonuclease digestion followed by high-throughput sequencing

ChIP-seq

ChIP-sequencing

DBD

DNA-binding domain

Dex

Dexamethasone

DHS

DNase I hypersensitive site

E2

Estradiol

ER

Estrogen receptor

GCs

Glucocorticoids

GRE

Glucocorticoid response elements

GR

Glucocorticoid receptor

GRBs

GR binding sites

nGREs

Negative glucocorticoid response elements

PTMs

Post-translational modifications

Pol II

RNA polymerase II

TADs

Topologically associated domains

TF

Transcription factor

TSS

Transcription start site

ZF

Zinc finger

Notes

Acknowledgements

We apologize to those authors whose articles we have not cited due to space constraints. This work is supported by the Israel Science Foundation (grant 748/14), Marie Curie Integration grant (CIG)- FP7-PEOPLE-20013-CIG-618763, the United States-Israel Bi-national Science Foundation (BSF) and I-CORE Program of the Planning and Budgeting Committee, and The Israel Science Foundation grant no. 41/11.

Supplementary material

709_2016_1063_MOESM1_ESM.docx (57 kb)
ESM 1 (DOCX 56 kb)

References

  1. Addison T (1855) On the constitutional and local effects of disease of the supra-renal capsules, 1 ed. Samuel Highley, LondonGoogle Scholar
  2. Alangari AA (2010) Genomic and non-genomic actions of glucocorticoids in asthma. Ann Thorac Med 5:133–139. doi: 10.4103/1817-1737.65040 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Beato M (1989) Gene regulation by steroid hormones. Cell 56:335–344. doi: 10.1016/0092-8674(89)90237-7 CrossRefPubMedGoogle Scholar
  4. Beato M, Herrlich P, Schütz G (1995) Steroid hormone receptors: many actors in search of a plot. Cell 83:851–857. doi: 10.1016/0092-8674(95)90201-5 CrossRefPubMedGoogle Scholar
  5. Biddie S, John S, Sabo P et al (2011) Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol Cell 43:145–155. doi: 10.1016/j.molcel.2011.06.016
  6. Bledsoe RK, Montana VG, Stanley TB et al (2002) Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 110:93–105. doi: 10.1016/S0092-8674(02)00817-6 CrossRefPubMedGoogle Scholar
  7. Burns CM (2016) The history of cortisone discovery and development. Rheum Dis Clin N Am 42:1–14. doi: 10.1016/j.rdc.2015.08.001 CrossRefGoogle Scholar
  8. Carnes M, Lent S, Feyzi J, Hazel D (1989) Plasma adrenocorticotropic hormone in the rat demonstrates three different rhythms within 24 h. Neuroendocrinology 50:17–25. doi: 10.1159/000125197 CrossRefPubMedGoogle Scholar
  9. Carroll JS, Meyer CA, Song J et al (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38:1289–1297. doi: 10.1038/ng1901 CrossRefPubMedGoogle Scholar
  10. Cheung J, Smith DF (2000) Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 14:939–946. doi: 10.1210/mend.14.7.0489 CrossRefPubMedGoogle Scholar
  11. Chinenov Y, Coppo M, Gupte R et al (2014) Glucocorticoid receptor coordinates transcription factor-dominated regulatory network in macrophages. BMC Genomics 15(656). doi: 10.1186/1471-2164-15-656
  12. Chung S, Son GH, Kim K (2011) Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications. Biochim Biophys Acta Mol basis Dis 1812:581–591. doi: 10.1016/j.bbadis.2011.02.003 CrossRefGoogle Scholar
  13. Cirillo LA, Mcpherson CE, Bossard P et al (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome. EMBO J 17:244–254CrossRefPubMedPubMedCentralGoogle Scholar
  14. Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304. doi: 10.1146/annurev.biochem.77.062706.153223 CrossRefPubMedGoogle Scholar
  15. Cole TJ, Blendy JA, Monaghan AP et al (1995) Molecular genetic analysis of glucocorticoid signaling during mouse development. Steroids 60:93–96CrossRefPubMedGoogle Scholar
  16. Coolens JL, Van Baelen H, Heyns W (1987) Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem 26:197–202CrossRefPubMedGoogle Scholar
  17. Coulon A, Chow CC, Singer RH, Larson DR (2013) Eukaryotic transcriptional dynamics: from single molecules to cell populations. Nat Rev Genet 14:572–584. doi: 10.1038/nrg3484 CrossRefPubMedGoogle Scholar
  18. Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 335:2–13. doi: 10.1016/j.mce.2010.04.005 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Cushing H (1932) The basophil adenomas of the pitiutary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp 50:180–181Google Scholar
  20. Diamond MI, Miner JN, Yoshinaga SK, Yamamoto KR (1990) Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science 249(80):1266–1272CrossRefPubMedGoogle Scholar
  21. Dixon JR, Selvaraj S, Yue F et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380. doi: 10.1038/nature11082 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Freedman LP, Luisi BF, Korszun ZR et al (1988) The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature 334:543–546. doi: 10.1038/334543a0 CrossRefPubMedGoogle Scholar
  23. Glass CK, Saijo K (2010) Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol 10:365–376. doi: 10.1038/nri2748 CrossRefPubMedGoogle Scholar
  24. Greenstein S, Ghias K, Krett NL, Rosen ST (2002) Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies. Clin Cancer Res 8:1681–1694PubMedGoogle Scholar
  25. Grøntved L, John S, Baek S et al (2013) C/EBP maintains chromatin accessibility in liver and facilitates glucocorticoid receptor recruitment to steroid response elements. EMBO J 32:1568–1583. doi: 10.1038/emboj.2013.106 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Guertin MJ, Zhang X, Coonrod SA, Hager GL (2014) Transient estrogen receptor binding and p300 redistribution support a squelching mechanism for estradiol-repressed genes. Mol Endocrinol 28:1522–1533. doi: 10.1210/me.2014-1130 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hager GL, Elbi C, Johnson TA et al (2006) Chromatin dynamics and the evolution of alternate promoter states. Chromosom Res 14:107–116. doi: 10.1007/s10577-006-1030-0 CrossRefGoogle Scholar
  28. Hah N, Murakami S, Nagari A et al (2013) Enhancer transcripts mark active estrogen receptor binding sites. Genome Res 23:1210–1223. doi: 10.1101/gr.152306.112 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hakim O, John S, Ling JQ et al (2009) Glucocorticoid receptor activation of the Ciz1-Lcn2 locus by long range interactions. J Biol Chem 284:6048–6052. doi: 10.1074/jbc.C800212200 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Hay D, Hughes JR, Babbs C et al (2016) Genetic dissection of the α-globin super-enhancer in vivo. Nat Genet 48:895–903. doi: 10.1038/ng.3605 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Herrlich P (2001) Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20:2465–2475. doi: 10.1038/sj.onc.1204388 CrossRefPubMedGoogle Scholar
  32. Hua G, Paulen L, Chambon P et al (2016) GR SUMOylation and formation of an SUMO-SMRT/ NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression. Proc Natl Acad Sci 113(5):E626–E634. doi: 10.1073/pnas.1522821113 CrossRefPubMedGoogle Scholar
  33. Jiang C, Pugh BF (2009) Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet 10:161–172. doi: 10.1038/nrg2522 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Jin F, Li Y, Dixon JR et al (2013) A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503:290–294. doi: 10.1038/nature12644 PubMedPubMedCentralGoogle Scholar
  35. John S, Johnson TA, Sung M-H et al (2009) Kinetic complexity of the global response to glucocorticoid receptor action. Endocrinology 150:1766–1774. doi: 10.1210/en.2008-0863 CrossRefPubMedPubMedCentralGoogle Scholar
  36. John S, Sabo PJ, Johnson TA et al (2008) Interaction of the glucocorticoid receptor with the chromatin landscape. Mol Cell 29:611–624. doi: 10.1016/j.molcel.2008.02.010 CrossRefPubMedGoogle Scholar
  37. John S, Sabo PJ, Thurman RE et al (2011) Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet 43:264–268. doi: 10.1038/ng.759 CrossRefPubMedGoogle Scholar
  38. Kadmiel M, Cidlowski JA (2013) Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 34:518–530. doi: 10.1016/j.tips.2013.07.003 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Kuznetsova T, Wang S-Y, Rao NA et al (2015) Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization. Genome Biol 16(264). doi: 10.1186/s13059-015-0832-9
  40. Langlais D, Couture C, Balsalobre A et al (2012) The Stat3/GR interaction code: predictive value of direct/indirect DNA recruitment for transcription outcome. Mol Cell 47:38–49. doi: 10.1016/j.molcel.2012.04.021 CrossRefPubMedGoogle Scholar
  41. Le Dily F, Baù D, Pohl A et al (2014) Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation. Genes Dev 28:2151–2162. doi: 10.1101/gad.241422.114 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Le Dily F, Beato M (2015) TADs as modular and dynamic units for gene regulation by hormones. FEBS Lett 589:2885–2892. doi: 10.1016/j.febslet.2015.05.026 CrossRefPubMedGoogle Scholar
  43. Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719CrossRefPubMedGoogle Scholar
  44. Li Q, Wrange O (1995) Accessibility of a glucocorticoid response element in a nucleosome depends on its rotational positioning. Mol Cell Biol 15:4375–4384CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lim H-W, Uhlenhaut NH, Rauch A et al (2015) Genomic redistribution of GR monomers and dimers mediates transcriptional response to exogenous glucocorticoid in vivo. Genome Res 25:836–844. doi: 10.1101/gr.188581.114 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lin K-T, Wang L-H (2016) New dimension of glucocorticoids in cancer treatment. Steroids 111:84–88. doi: 10.1016/j.steroids.2016.02.019 CrossRefPubMedGoogle Scholar
  47. Luca F, Maranville JC, Richards AL et al (2013) Genetic, functional and molecular features of glucocorticoid receptor binding. PLoS One 8:e61654. doi: 10.1371/journal.pone.0061654 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Luisi BF, WX X, Otwinowski Z et al (1991) Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352:497–505. doi: 10.1038/352497a0 CrossRefPubMedGoogle Scholar
  49. Melters DP, Nye J, Zhao H, Dalal Y (2015) Chromatin dynamics in vivo: a game of musical chairs. Genes (Basel) 6:751–776. doi: 10.3390/genes6030751 Google Scholar
  50. Meyer ME, Gronemeyer H, Turcotte B et al (1989) Steroid hormone receptors compete for factors that mediate their enhancer function. Cell 57:433–442CrossRefPubMedGoogle Scholar
  51. Morris SA, Baek S, Sung M-H et al (2014) Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions. Nat Struct Mol Biol 21:73–81. doi: 10.1038/nsmb.2718 CrossRefPubMedGoogle Scholar
  52. Nagaich AK, Walker DA, Wolford R, Hager GL (2004) Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling. Mol Cell 14:163–174CrossRefPubMedGoogle Scholar
  53. Nora EP, Lajoie BR, Schulz EG et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385. doi: 10.1038/nature11049 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Ostuni R, Piccolo V, Barozzi I et al (2013) Latent enhancers activated by stimulation in differentiated cells. Cell 152:157–171. doi: 10.1016/j.cell.2012.12.018 CrossRefPubMedGoogle Scholar
  55. Pan D, Kocherginsky M, Conzen SD (2011) Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer Res 71:6360–6370. doi: 10.1158/0008-5472.CAN-11-0362 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Polman JAE, Welten JE, Bosch DS et al (2012) A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells. BMC Neurosci 13(118). doi: 10.1186/1471-2202-13-118
  57. Presman DM, Ganguly S, Schiltz RL et al (2016) DNA binding triggers tetramerization of the glucocorticoid receptor in live cells. Proc Natl Acad Sci U S A 113:8236–8241. doi: 10.1073/pnas.1606774113 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Ramamoorthy S, Cidlowski JA (2013) Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements. Mol Cell Biol 33:1711–1722. doi: 10.1128/MCB.01151-12 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Rao NAS, McCalman MT, Moulos P et al (2011) Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes. Genome Res 21:1404–1416. doi: 10.1101/gr.118042.110 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Reddy TE, Pauli F, Sprouse RO et al (2009) Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation. Genome Res 19:2163–2171. doi: 10.1101/gr.097022.109 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Richard-Foy H, Hager GL (1987) Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J 6:2321–2328PubMedPubMedCentralGoogle Scholar
  62. Rogatsky I, Luecke HF, Leitman DC, Yamamoto KR (2002) Alternate surfaces of transcriptional coregulator GRIP1 function in different glucocorticoid receptor activation and repression contexts. Proc Natl Acad Sci U S A 99:16701–16706. doi: 10.1073/pnas.262671599 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Roqueta-Rivera M, Esquejo RM, Phelan PE et al (2016) SETDB2 links glucocorticoid to lipid metabolism through Insig2a regulation. Cell Metab 24:474–484. doi: 10.1016/j.cmet.2016.07.025
  64. Sacta MA, Chinenov Y, Rogatsky I (2016) Glucocorticoid signaling: an update from a genomic perspective. Annu Rev Physiol 78:155–180. doi: 10.1146/annurev-physiol-021115-105323 CrossRefPubMedGoogle Scholar
  65. Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489:109–113. doi: 10.1038/nature11279 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89. doi: 10.1210/edrv.21.1.0389 PubMedGoogle Scholar
  67. Sasse SK, Zuo Z, Kadiyala V et al (2015) Response element composition governs correlations between binding site affinity and transcription in glucocorticoid receptor feed-forward loops. J Biol Chem 290:19756–19769. doi: 10.1074/jbc.M115.668558 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Schäcke H, Döcke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23–43CrossRefPubMedGoogle Scholar
  69. Schiller BJ, Chodankar R, Watson LC et al (2014) Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes. Genome Biol 15(418). doi: 10.1186/s13059-014-0418-y
  70. Shin HY, Willi M, Yoo KH et al (2016) Hierarchy within the mammary STAT5-driven Wap super-enhancer. Nat Genet 48:904–911. doi: 10.1038/ng.3606 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Shipp LE, Lee JV, C-Y Y et al (2010) Transcriptional regulation of human dual specificity protein phosphatase 1 (DUSP1) gene by glucocorticoids. PLoS One 5:e13754. doi: 10.1371/journal.pone.0013754 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Shlyueva D, Stampfel G, Stark A (2014) Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 15:272–286. doi: 10.1038/nrg3682 CrossRefPubMedGoogle Scholar
  73. Soufi A, Donahue G, Zaret KS et al (2012) Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151:994–1004. doi: 10.1016/j.cell.2012.09.045 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Soufi A, Garcia MF, Jaroszewicz A et al (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161:555–568. doi: 10.1016/j.cell.2015.03.017 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Stahn C, Buttgereit F (2008) Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol 4:525–533. doi: 10.1038/ncprheum0898 CrossRefPubMedGoogle Scholar
  76. Starick SR, Ibn-Salem J, Jurk M et al (2015) ChIP-exo signal associated with DNA-binding motifs provide insights into the genomic binding of the glucocorticoid receptor and cooperating transcription factors. Genome Res 25:825–835. doi: 10.1101/gr.185157.114 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Stavreva DA, Coulon A, Baek S et al (2015) Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing. Genome Res 25:845–857. doi: 10.1101/gr.184168.114
  78. Stavreva DA, Wiench M, John S et al (2009) Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol 11:1093–1102. doi: 10.1038/ncb1922 CrossRefPubMedGoogle Scholar
  79. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45. doi: 10.1038/47412 CrossRefPubMedGoogle Scholar
  80. Surjit M, Ganti KP, Mukherji A et al (2011) Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor. Cell 145:224–241. doi: 10.1016/j.cell.2011.03.027 CrossRefPubMedGoogle Scholar
  81. Swinstead EE, Miranda TB, Paakinaho V et al (2016a) Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions. Cell 165:593–605. doi: 10.1016/j.cell.2016.02.067 CrossRefPubMedGoogle Scholar
  82. Swinstead EE, Paakinaho V, Presman DM, Hager GL (2016b) Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: a new perspective: multiple transcription factors can effect chromatin pioneer functions through dynamic interactions with ATP-dependent chromatin remodeling factors. BioEssays 38:1150–1157. doi: 10.1002/bies.201600137 CrossRefPubMedGoogle Scholar
  83. Thurman RE, Rynes E, Humbert R et al (2012) The accessible chromatin landscape of the human genome. Nature 489:75–82. doi: 10.1038/nature11232 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Uhlenhaut NH, Barish GD, RT Y et al (2013) Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes. Mol Cell 49:158–171. doi: 10.1016/j.molcel.2012.10.013 CrossRefPubMedGoogle Scholar
  85. van der Laan S, de Kloet ER, Meijer OC (2009) Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene. PLoS One 4:e4327. doi: 10.1371/journal.pone.0004327 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Vandevyver S, Dejager L, Libert C (2012) On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic 13:364–374. doi: 10.1111/j.1600-0854.2011.01288.x CrossRefPubMedGoogle Scholar
  87. Vockley CM, D’Ippolito AM, McDowell IC et al (2016) Direct GR binding sites potentiate clusters of TF binding across the human genome. Cell 166:1269–1281. doi: 10.1016/j.cell.2016.07.049 CrossRefPubMedGoogle Scholar
  88. Voss TC, John S, Hager GL (2006) Single-cell analysis of glucocorticoid receptor action reveals that stochastic post-chromatin association mechanisms regulate ligand-specific transcription. MolEndocrinol 20:2641–2655Google Scholar
  89. Voss TC, Schiltz RL, Sung M-H et al (2011) Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell 146:544–554. doi: 10.1016/j.cell.2011.07.006 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Voss TC, Schiltz RL, Sung M-H et al (2009) Combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity. J Cell Sci 122:345–356. doi: 10.1242/jcs.035865 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Weinberger C, Hollenberg SM, Rosenfeld MG, Evans RM (1985) Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature 318:670–672CrossRefPubMedGoogle Scholar
  92. Wiench M, John S, Baek S et al (2011) DNA methylation status predicts cell type-specific enhancer activity. EMBO J 30:3028–3039. doi: 10.1038/emboj.2011.210 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Young EA, Abelson J, Lightman SL (2004) Cortisol pulsatility and its role in stress regulation and health. Front Neuroendocr 25:69–76. doi: 10.1016/j.yfrne.2004.07.001 CrossRefGoogle Scholar
  94. Yu C-Y, Mayba O, Lee JV et al (2010) Genome-wide analysis of glucocorticoid receptor binding regions in adipocytes reveal gene network involved in triglyceride homeostasis. PLoS One 5:e15188. doi: 10.1371/journal.pone.0015188 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Zaret KS, Carroll JS (2011) Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25:2227–2241. doi: 10.1101/gad.176826.111 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Zaret KS, Yamamoto KR (1984) Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element. Cell 38:29–38CrossRefPubMedGoogle Scholar
  97. Zen M, Canova M, Campana C et al (2011) The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev 10:305–310. doi: 10.1016/j.autrev.2010.11.009 CrossRefPubMedGoogle Scholar
  98. Zhang X, Choi PS, Francis JM et al (2015) Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat Genet 48:1–8. doi: 10.1038/ng.3470 CrossRefGoogle Scholar

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© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.The Mina and Everard Goodman Faculty of Life SciencesBar-Ilan UniversityRamat-GanIsrael

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