Skip to main content Accessibility help
×
Home

Interrogating the genome to understand oestrogen-receptor-mediated transcription

  • Sara C. Dietz (a1) and Jason S. Carroll (a1)

Abstract

Defining transcription mediated by the oestrogen (estrogen) receptor (ER) in breast cancer cell models has been an area of interest for many years. Initial studies focused on promoter regions of putative target genes and revealed significant insight into the basis of ER binding to DNA. More recently, the complexities of ER transcription are starting to become apparent. It is now clear that ER can regulate gene targets from significant distances and that cooperating transcription factors play an integral role in ER activity. It is also clear that the sequence information defining an in vivo ER-binding site is more complicated than initially thought. However, contemporary genomic tools based on chromatin immunoprecipitation (ChIP) – such as ChIP-on-chip and ChIP–sequencing – and gene expression profiling have allowed us to redefine the underlying properties of ER biology on a genomic scale. The advances in technology that have permitted a better understanding of how and where ER can bind to DNA are discussed in this review. The possible clinical implications of these findings for understanding the role of oestrogen in breast cancer are also briefly considered.

Copyright

Corresponding author

*Corresponding author: Jason S. Carroll, Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. Tel:  + 44 (0)1223 404510; Fax:  + 44 (0)1223 404199; E-mail: jason.carroll@cancer.org.uk

References

Hide All
1Osborne, C.K. (1998) Tamoxifen in the treatment of breast cancer. N Engl J Med 339, 1609-1618
2MacGregor, J.I. and Jordan, V.C. (1998) Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 50, 151-196
3Jordan, V.C. (2003) Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2, 205-213
4Anzick, S.L. et al. (1997) AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965-968
5Lavinsky, R.M. et al. (1998) Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes. Proc Natl Acad Sci U S A 95, 2920-2925
6Shang, Y. and Brown, M. (2002) Molecular determinants for the tissue specificity of SERMs. Science 295, 2465-2468
7Torres-Arzayus, M.I. et al. (2004) High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 6, 263-274
8Klinge, C.M. (2001) Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 29, 2905-2919
9Klein-Hitpass, L. et al. (1986) An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell 46, 1053-1061
10Berry, M., Nunez, A.M. and Chambon, P. (1989) Estrogen-responsive element of the human pS2 gene is an imperfectly palindromic sequence. Proc Natl Acad Sci U S A 86, 1218-1222
11Brown, A.M. et al. (1984) Activation of pS2 gene transcription is a primary response to estrogen in the human breast cancer cell line MCF-7. Proc Natl Acad Sci U S A 81, 6344-6348
12Ikeda, K. et al. (2000) Promoter analysis and chromosomal mapping of human EBAG9 gene. Biochem Biophys Res Commun 273, 654-660
13Cavailles, V., Augereau, P. and Rochefort, H. (1993) Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells. Proc Natl Acad Sci U S A 90, 203-207
14Krishnan, V., Wang, X. and Safe, S. (1994) Estrogen receptor-Sp1 complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 human breast cancer cells. J Biol Chem 269, 15912-15917
15Wang, F. et al. (1997) Identification of a functional imperfect estrogen-responsive element in the 5'-promoter region of the human cathepsin D gene. Biochemistry 36, 7793-7801
16Prall, O.W. et al. (1998) c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry. Mol Cell Biol 18, 4499-4508
17Cheung, E., Schwabish, M.A. and Kraus, W.L. (2003) Chromatin exposes intrinsic differences in the transcriptional activities of estrogen receptors alpha and beta. EMBO J 22, 600-611
18Shang, Y. et al. (2000) Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103, 843-852
19Metivier, R. et al. (2003) Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751-763
20Stenoien, D.L. et al. (2001) Ligand-mediated assembly and real-time cellular dynamics of estrogen receptor alpha-coactivator complexes in living cells. Mol Cell Biol 21, 4404-4412
21Becker, M. et al. (2002) Dynamic behavior of transcription factors on a natural promoter in living cells. EMBO Rep 3, 1188-1194
22Bajic, V.B. et al. (2003) Dragon ERE Finder version 2: A tool for accurate detection and analysis of estrogen response elements in vertebrate genomes. Nucleic Acids Res 31, 3605-3607
23Lin, C.Y. et al. (2004) Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biol 5, R66
24Kamalakaran, S., Radhakrishnan, S.K. and Beck, W.T. (2005) Identification of estrogen-responsive genes using a genome-wide analysis of promoter elements for transcription factor binding sites. J Biol Chem 280, 21491-21497
25Cavailles, V. et al. (1995) Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J 14, 3741-3751
26Wei, L.N. et al. (2000) Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing. J Biol Chem 275, 40782-40787
27Forrester, W.C. et al. (1990) A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev 4, 1637-1649
28Kim, C.G. et al. (1992) Inactivation of the human beta-globin gene by targeted insertion into the beta-globin locus control region. Genes Dev 6, 928-938
29Aladjem, M.I. et al. (1995) Participation of the human beta-globin locus control region in initiation of DNA replication. Science 270, 815-819
30Sawado, T. et al. (2003) The beta -globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation. Genes Dev 17, 1009-1018
31Bourdeau, V. et al. (2004) Genome-wide identification of high-affinity estrogen response elements in human and mouse. Mol Endocrinol 18, 1411-1427
32Vega, V.B. et al. (2006) Multi-platform genome-wide identification and modeling of functional human estrogen receptor binding sites. Genome Biol 7, R82
33Davis, D.L. and Burch, J.B. (1996) The chicken vitellogenin II gene is flanked by a GATA factor-dependent estrogen response unit. Mol Endocrinol 10, 937-944
34Dellovade, T.L. et al. (1996) Thyroid hormone and estrogen interact to regulate behavior. Proc Natl Acad Sci U S A 93, 12581-12586
35Batistuzzo de Medeiros, S.R. et al. (1997) Functional interactions between the estrogen receptor and the transcription activator Sp1 regulate the estrogen-dependent transcriptional activity of the vitellogenin A1 io promoter. J Biol Chem 272, 18250-18260
36Wang, F., Samudio, I. and Safe, S. (2001) Transcriptional activation of rat creatine kinase B by 17beta-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites. J Cell Biochem 84, 156-172
37Wang, F. et al. (1998) Functional and physical interactions between the estrogen receptor Sp1 and nuclear aryl hydrocarbon receptor complexes. Nucleic Acids Res 26, 3044-3052
38Garcia-Arencibia, M. et al. (2005) Identification of two functional estrogen response elements complexed with AP-1-like sites in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol 94, 1-14
39Blanchette, M. et al. (2006) Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression. Genome Res 16, 656-668
40Laganiere, J., Deblois, G. and Giguere, V. (2005) Functional genomics identifies a mechanism for estrogen activation of the retinoic acid receptor alpha1 gene in breast cancer cells. Mol Endocrinol 19, 1584-1592
41Impey, S. et al. (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119, 1041-1054
42Wei, C.L. et al. (2006) A global map of p53 transcription-factor binding sites in the human genome. Cell 124, 207-219
43Lin, C.Y. et al. (2007) Whole-genome cartography of estrogen receptor alpha binding sites. PLoS Genet 3, e87
44Ng, P. et al. (2006) Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res 34, e84
45Carroll, J.S. et al. (2005) Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell 122, 33-43
46Laganiere, J. et al. (2005) Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Proc Natl Acad Sci U S A 102, 11651-11656
47Cheng, A.S. et al. (2006) Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Mol Cell 21, 393-404
48Kwon, Y.S. et al. (2007) Sensitive ChIP-DSL technology reveals an extensive estrogen receptor {alpha}-binding program on human gene promoters. Proc Natl Acad Sci U S A 104, 4852-4857
49Carroll, J.S. et al. (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38, 1289-1297
50Frasor, J. et al. (2003) Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology 144, 4562-4574
51Teyssier, C. et al. (2003) Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-induced activator protein-1 activity by reversing glucocorticoid receptor-interacting protein 1 effect. Mol Endocrinol 17, 287-299
52Kim, T.H. et al. (2005) A high-resolution map of active promoters in the human genome. Nature 436, 876-880
53Yang, A. et al. (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24, 593-602
54Kim, T.H. et al. (2007) Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell 128, 1231-1245
55Mikkelsen, T.S. et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553-560
56Johnson, D.S. et al. (2007) Genome-wide mapping of in vivo protein-DNA interactions. Science 316, 1497-1502
57Odom, D.T. et al. (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39, 730-732
58Gao, H. et al. (2008) Genome-wide identification of estrogen receptor {alpha}-binding sites in mouse liver. Mol Endocrinol 22, 10-22
59Ballestar, E. et al. (2003) Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J 22, 6335-6345
60Miao, F. and Natarajan, R. (2005) Mapping global histone methylation patterns in the coding regions of human genes. Mol Cell Biol 25, 4650-4661
61Bernstein, B.E. et al. (2005) Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120, 169-181
62Huebert, D.J. et al. (2006) Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 40, 365-369
63Lupien, M. et al. FoxA1 translates epigenetic signatures into enhancer driven lineage-specific transcription. Cell (in press)
64Bender, M.A. et al. (2000) Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region. Mol Cell 5, 387-393
65Schubeler, D., Groudine, M. and Bender, M.A. (2001) The murine beta-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes. Proc Natl Acad Sci U S A 98, 11432-11437
66Cohen, A. et al. (2007) Alterations in microRNA expression profiles reveal a novel pathway for estrogen regulation. Endocrinology Dec 20; [Epub ahead of print]
67Iorio, M.V. et al. (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65, 7065-7070
68Ma, L., Teruya-Feldstein, J. and Weinberg, R.A. (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688
69Wang, Q., Carroll, J.S. and Brown, M. (2005) Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell 19, 631-642
70Dekker, J. et al. (2002) Capturing chromosome conformation. Science 295, 1306-1311
71Dostie, J. et al. (2006) Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16, 1299-1309
72Zhao, Z. et al. (2006) Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet 38, 1341-1347
73Simonis, M. et al. (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet 38, 1348-1354
74O'Neill, L.P., VerMilyea, M.D. and Turner, B.M. (2006) Epigenetic characterization of the early embryo with a chromatin immunoprecipitation protocol applicable to small cell populations. Nat Genet 38, 835-841
75Easton, D.F. et al. (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447, 1087-1093
76Badve, S. et al. (2007) FOXA1 expression in breast cancer–correlation with luminal subtype A and survival. Clin Cancer Res 13, 4415-4421
77Howell, A. et al. (1996) Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. Br J Cancer 74, 300-308
78Johnston, S.R. (1997) Acquired tamoxifen resistance in human breast cancer–potential mechanisms and clinical implications. Anticancer Drugs 8, 911-930
79Johnston, S.R. et al. (1995) Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. Cancer Res 55, 3331-3338
Baek, S.H. and Rosenfeld, M.G. (2004) Nuclear receptor coregulators: their modification codes and regulatory mechanism by translocation. Biochem Biophys Res Commun 319, 707-714
Buck, M.J. and Lieb, J.D. (2004) ChIP-on-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 83, 349-360
Hudson, M.E. and Snyder, M. (2006) High-throughput methods of regulatory element discovery. Biotechniques 41, 673, 675, 677 passim

The NURSA website provides the most extensive information on nuclear receptors and their transcriptional properties:

Interrogating the genome to understand oestrogen-receptor-mediated transcription

  • Sara C. Dietz (a1) and Jason S. Carroll (a1)

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed