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Review
. 2008 Feb 15:6:e005.
doi: 10.1621/nrs.06005.

A global view of transcriptional regulation by nuclear receptors: gene expression, factor localization, and DNA sequence analysis

Miltiadis Kininis  1 , W Lee Kraus
Affiliations
Review

A global view of transcriptional regulation by nuclear receptors: gene expression, factor localization, and DNA sequence analysis

Miltiadis Kininis et al. Nucl Recept Signal. .

Abstract

Recent genomic analyses of transcription factor binding, histone modification, and gene expression have provided a global view of transcriptional regulation by nuclear receptors (NRs) that complements an existing large body of literature on gene-specific studies. The picture emerging from these genomic studies indicates that NRs bind at promoter-proximal and promoter-distal enhancers in conjunction with other transcription factors (e.g., activator protein-1, Sp1 and FOXA1). This binding promotes the recruitment of coregulators that mediate the posttranslational modification of histones at promoters and enhancers. Ultimately, signaling through liganded NRs stimulates changes in the occupancy of RNA polymerase II (Pol II) or the activation of preloaded Pol II at target promoters. Chromosomal looping and/or Pol II tracking may underlie promoter-enhancer communication. Interestingly, the direct target genes of NR signaling represent a limited subset of all the genes regulated by NR ligands, with the rest being regulated through secondary effects. As suggested by previous gene-specific analyses, NR-mediated outcomes are highly cell type- and promoter-specific, highlighting the complexity of transcriptional regulation by NRs and the value of genomic analyses for identifying commonly shared patterns. Overall, NRs share common themes in their patterns of localization and transcriptional regulation across mammalian genomes. In this review, we provide an overview of recent advances in the understanding of NR-mediated transcription garnered from genomic analyses of gene expression, factor localization, and target DNA sequences.

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Figures

Figure 1
Figure 1. Transcriptional regulation by nuclear receptors.
Transcriptional regulation by NRs is a multistep process involving: (1) the binding of liganded NRs to promoter-proximal and promoter-distal enhancers in conjunction with other transcription factors (e.g., AP1, Sp1 and FOXA1), (2) the ligand-dependent recruitment and actions of coregulators (coactivators and corepressors) to modify chromatin and associated factors, and (3) the regulation of Pol II binding or the activation of preloaded Pol II at target promoters.
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References

    1. Acevedo M. L., Kraus W. L. Transcriptional activation by nuclear receptors. Essays Biochem. 2004;40:73–88. - PubMed
    1. Aiyar S. E., Sun J. L., Blair A. L., Moskaluk C. A., Lu Y. Z., Ye Q. N., Yamaguchi Y., Mukherjee A., Ren D. M., Handa H., Li R. Attenuation of estrogen receptor α-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes Dev. 2004;18:2134–46. - PMC - PubMed
    1. Barski A., Cuddapah S., Cui K., Roh T. Y., Schones D. E., Wang Z., Wei G., Chepelev I., Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–37. - PubMed
    1. Berger S. L. The complex language of chromatin regulation during transcription. Nature. 2007;447:407–12. - PubMed
    1. Birney E., Stamatoyannopoulos J. A., Dutta A., Guigo R., Gingeras T. R., Margulies E. H., Weng Z., Snyder M., Dermitzakis E. T., Thurman R. E., Kuehn M. S., Taylor C. M., Neph S., Koch C. M., Asthana S., Malhotra A., Adzhubei I., Greenbaum J. A., Andrews R. M., Flicek P., Boyle P. J., Cao H., Carter N. P., Clelland G. K., Davis S., Day N., Dhami P., Dillon S. C., Dorschner M. O., Fiegler H., Giresi P. G., Goldy J., Hawrylycz M., Haydock A., Humbert R., James K. D., Johnson B. E., Johnson E. M., Frum T. T., Rosenzweig E. R., Karnani N., Lee K., Lefebvre G. C., Navas P. A., Neri F., Parker S. C., Sabo P. J., Sandstrom R., Shafer A., Vetrie D., Weaver M., Wilcox S., Yu M., Collins F. S., Dekker J., Lieb J. D., Tullius T. D., Crawford G. E., Sunyaev S., Noble W. S., Dunham I., Denoeud F., Reymond A., Kapranov P., Rozowsky J., Zheng D., Castelo R., Frankish A., Harrow J., Ghosh S., Sandelin A., Hofacker I. L., Baertsch R., Keefe D., Dike S., Cheng J., Hirsch H. A., Sekinger E. A., Lagarde J., Abril J. F., Shahab A., Flamm C., Fried C., Hackermuller J., Hertel J., Lindemeyer M., Missal K., Tanzer A., Washietl S., Korbel J., Emanuelsson O., Pedersen J. S., Holroyd N., Taylor R., Swarbreck D., Matthews N., Dickson M. C., Thomas D. J., Weirauch M. T., Gilbert J., Drenkow J., Bell I., Zhao X., Srinivasan K. G., Sung W. K., Ooi H. S., Chiu K. P., Foissac S., Alioto T., Brent M., Pachter L., Tress M. L., Valencia A., Choo S. W., Choo C. Y., Ucla C., Manzano C., Wyss C., Cheung E., Clark T. G., Brown J. B., Ganesh M., Patel S., Tammana H., Chrast J., Henrichsen C. N., Kai C., Kawai J., Nagalakshmi U., Wu J., Lian Z., Lian J., Newburger P., Zhang X., Bickel P., Mattick J. S., Carninci P., Hayashizaki Y., Weissman S., Hubbard T., Myers R. M., Rogers J., Stadler P. F., Lowe T. M., Wei C. L., Ruan Y., Struhl K., Gerstein M., Antonarakis S. E., Fu Y., Green E. D., Karaoz U., Siepel A., Taylor J., Liefer L. A., Wetterstrand K. A., Good P. J., Feingold E. A., Guyer M. S., Cooper G. M., Asimenos G., Dewey C. N., Hou M., Nikolaev S., Montoya-Burgos J. I., Loytynoja A., Whelan S., Pardi F., Massingham T., Huang H., Zhang N. R., Holmes I., Mullikin J. C., Ureta-Vidal A., Paten B., Seringhaus M., Church D., Rosenbloom K., Kent W. J., Stone E. A., Batzoglou S., Goldman N., Hardison R. C., Haussler D., Miller W., Sidow A., Trinklein N. D., Zhang Z. D., Barrera L., Stuart R., King D. C., Ameur A., Enroth S., Bieda M. C., Kim J., Bhinge A. A., Jiang N., Liu J., Yao F., Vega V. B., Lee C. W., Ng P., Shahab A., Yang A., Moqtaderi Z., Zhu Z., Xu X., Squazzo S., Oberley M. J., Inman D., Singer M. A., Richmond T. A., Munn K. J., Rada-Iglesias A., Wallerman O., Komorowski J., Fowler J. C., Couttet P., Bruce A. W., Dovey O. M., Ellis P. D., Langford C. F., Nix D. A., Euskirchen G., Hartman S., Urban A. E., Kraus P., Van Calcar S., Heintzman N., Kim T. H., Wang K., Qu C., Hon G., Luna R., Glass C. K., Rosenfeld M. G., Aldred S. F., Cooper S. J., Halees A., Lin J. M., Shulha H. P., Zhang X., Xu M., Haidar J. N., Yu Y., Ruan Y., Iyer V. R., Green R. D., Wadelius C., Farnham P. J., Ren B., Harte R. A., Hinrichs A. S., Trumbower H., Clawson H., Hillman-Jackson J., Zweig A. S., Smith K., Thakkapallayil A., Barber G., Kuhn R. M., Karolchik D., Armengol L., Bird C. P., de Bakker P. I., Kern A. D., Lopez-Bigas N., Martin J. D., Stranger B. E., Woodroffe A., Davydov E., Dimas A., Eyras E., Hallgrimsdottir I. B., Huppert J., Zody M. C., Abecasis G. R., Estivill X., Bouffard G. G., Guan X., Hansen N. F., Idol J. R., Maduro V. V., Maskeri B., McDowell J. C., Park M., Thomas P. J., Young A. C., Blakesley R. W., Muzny D. M., Sodergren E., Wheeler D. A., Worley K. C., Jiang H., Weinstock G. M., Gibbs R. A., Graves T., Fulton R., Mardis E. R., Wilson R. K., Clamp M., Cuff J., Gnerre S., Jaffe D. B., Chang J. L., Lindblad-Toh K., Lander E. S., Koriabine M., Nefedov M., Osoegawa K., Yoshinaga Y., Zhu B., de Jong P. J. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447:799–816. - PMC - PubMed

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