Skip to main content

Advertisement

Log in

Functional Genomic Methods to Study Estrogen Receptor Activity

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Estrogen Receptor (ER) is a nuclear receptor that mediates the actions of estrogen and tamoxifen. ER is expressed in a major fraction of human breast cancers. Recently, genomic maps for estrogen- and tamoxifen-ER have been published. Interestingly, estrogen and tamoxifen induce similar genomic interactions and both ligands have been shown to use co-operating factors. The interactions of these co-operating factors within ER regions have impact both on ER-DNA interactions and gene expression regulated by estrogen and tamoxifen. Moreover, the study of chromatin changes induced by these factors has also provided significant insight into our understanding of ER transcriptional regulation. This methods review describes some functional genomic methods to study the influence of both ER ligands and ER co-operating factors. The analysis of protein-DNA interactions and chromatin changes can be explored by using classical and novel methods such as Chromatin Immunoprecipitation (ChIP) or Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE). This review also explores the properties of each of these methods and the advantages of combining them with high throughput sequencing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

ER:

Estrogen receptor

ChIP:

Chromatin Inmunoprecipitation

FAIRE:

Formaldehyde-Assisted Isolation of Regulatory Elements

SERM:

Selective Estrogen Receptor Modulator

References

  1. Prat A, Baselga J. The role of hormonal therapy in the management of hormonal-receptor-positive breast cancer with co-expression of HER2. Nat Clin Pract Oncol. 2008;5:531.

    Article  PubMed  CAS  Google Scholar 

  2. Duong V, et al. ERalpha and ERbeta expression and transcriptional activity are differentially regulated by HDAC inhibitors. Oncogene. 2006;25:1799.

    Article  PubMed  CAS  Google Scholar 

  3. Frasor J, et al. 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. 2003;144:4562.

    Article  PubMed  CAS  Google Scholar 

  4. Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS. FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet. 2011;43:27.

    Article  PubMed  CAS  Google Scholar 

  5. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 2000;103:843.

    Article  PubMed  CAS  Google Scholar 

  6. Chang EC, Frasor J, Komm B, Katzenellenbogen BS. Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells. Endocrinology. 2006;147:4831.

    Article  PubMed  CAS  Google Scholar 

  7. Carroll JS, Brown M. Estrogen receptor target gene: an evolving concept. Mol Endocrinol. 2006;20:1707.

    Article  PubMed  CAS  Google Scholar 

  8. Narita M, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503.

    Article  PubMed  CAS  Google Scholar 

  9. Schmidt D, et al. ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions. Methods. 2009;48:240.

    Article  PubMed  CAS  Google Scholar 

  10. Hurtado A, et al. Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature. 2008;456:663.

    Article  PubMed  CAS  Google Scholar 

  11. Robinson JL, et al. Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO J. 2012;31:1617.

    Article  CAS  Google Scholar 

  12. Carroll JS, et al. Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006;38:1289.

    Article  PubMed  CAS  Google Scholar 

  13. Lin CY, et al. Whole-genome cartography of estrogen receptor alpha binding sites. PLoS Genet. 2007;3:e87.

    Article  PubMed  Google Scholar 

  14. Fullwood MJ, et al. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature. 2009;462:58.

    Article  PubMed  CAS  Google Scholar 

  15. Ross-Innes CS, et al. Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev. 2010;24:171.

    Article  PubMed  CAS  Google Scholar 

  16. Kong SL, Li G, Loh SL, Sung WK, Liu ET. Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a ligand-inducible growth state. Mol Syst Biol. 2011;7:526.

    Article  PubMed  Google Scholar 

  17. Lupien M, et al. Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance. Genes Dev. 2010;24:2219.

    Article  PubMed  CAS  Google Scholar 

  18. Ross-Innes CS, et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature. 2012;481:389.

    PubMed  CAS  Google Scholar 

  19. Welboren WJ, et al. ChIP-Seq of ERalpha and RNA polymerase II defines genes differentially responding to ligands. EMBO J. 2009;28:1418.

    Article  PubMed  CAS  Google Scholar 

  20. Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 2008;18:1851.

    Article  PubMed  CAS  Google Scholar 

  21. Hinrichs AS, et al. The UCSC genome browser database: update 2006. Nucleic Acids Res. 2006;34:D590.

    Article  PubMed  CAS  Google Scholar 

  22. Zhang Y, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9:R137.

    Article  PubMed  Google Scholar 

  23. Saldanha AJ. Java Treeview--extensible visualization of microarray data. Bioinformatics. 2004;20:3246.

    Article  PubMed  CAS  Google Scholar 

  24. Giresi PG, Lieb JD. Isolation of active regulatory elements from eukaryotic chromatin using FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements). Methods. 2009;48:233.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antoni Hurtado.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gilfillan, S., Fiorito, E. & Hurtado, A. Functional Genomic Methods to Study Estrogen Receptor Activity. J Mammary Gland Biol Neoplasia 17, 147–153 (2012). https://doi.org/10.1007/s10911-012-9254-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-012-9254-4

Keywords

Navigation