Coactivator function defines the active estrogen receptor alpha cistrome

Mathieu Lupien, Jérôme Eeckhoute, Clifford A. Meyer, Susan Miranda, Daniel R. Rhodes, X. Shirley Liu, Myles Brown

Research output: Contribution to journalArticle

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Abstract

Proper activation of transcriptional networks in complex organisms is central to the response to stimuli. We demonstrate that the selective activation of a subset of the estrogen receptor alpha (ERα) cistrome in MCF7 breast cancer cells provides specificity to the estradiol (E2) response. ERα-specific enhancers that are subject to E2-induced coactivator- associated arginine methyltransferase 1 (CARM1) action are critical to E2-stimulated gene expression. This is true for both FoxA1-dependent and independent enhancers. In contrast, a subset of E2-suppressed genes are controlled by FoxA1-independent ERα binding sites. Nonetheless, these are sites of E2-induced CARM1 activity. In addition, the MCF7 RNA polymerase II cistrome reveals preferential occupancy of E2-regulated promoters prior to stimulation. Interestingly, E2-suppressed genes tend to lie in otherwise silent genomic regions. Together, our results suggest that the transcriptional response to E2 in breast cancer cells is dependent on the interplay between polymerase II pre-occupied promoters and the subset of the ERα cistrome associated with coactivation.

Original languageEnglish (US)
Pages (from-to)3413-3423
Number of pages11
JournalMolecular and cellular biology
Volume29
Issue number12
DOIs
StatePublished - Jun 1 2009

Fingerprint

Estrogen Receptor alpha
Breast Neoplasms
RNA Polymerase II
Gene Regulatory Networks
Genes
Estradiol
Binding Sites
Gene Expression
coactivator-associated arginine methyltransferase 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Lupien, M., Eeckhoute, J., Meyer, C. A., Miranda, S., Rhodes, D. R., Liu, X. S., & Brown, M. (2009). Coactivator function defines the active estrogen receptor alpha cistrome. Molecular and cellular biology, 29(12), 3413-3423. https://doi.org/10.1128/MCB.00020-09

Coactivator function defines the active estrogen receptor alpha cistrome. / Lupien, Mathieu; Eeckhoute, Jérôme; Meyer, Clifford A.; Miranda, Susan; Rhodes, Daniel R.; Liu, X. Shirley; Brown, Myles.

In: Molecular and cellular biology, Vol. 29, No. 12, 01.06.2009, p. 3413-3423.

Research output: Contribution to journalArticle

Lupien, M, Eeckhoute, J, Meyer, CA, Miranda, S, Rhodes, DR, Liu, XS & Brown, M 2009, 'Coactivator function defines the active estrogen receptor alpha cistrome', Molecular and cellular biology, vol. 29, no. 12, pp. 3413-3423. https://doi.org/10.1128/MCB.00020-09
Lupien, Mathieu ; Eeckhoute, Jérôme ; Meyer, Clifford A. ; Miranda, Susan ; Rhodes, Daniel R. ; Liu, X. Shirley ; Brown, Myles. / Coactivator function defines the active estrogen receptor alpha cistrome. In: Molecular and cellular biology. 2009 ; Vol. 29, No. 12. pp. 3413-3423.
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