Journal article
Interaction of TFAP2C with the Estrogen Receptor-α Promoter Is Controlled by Chromatin Structure
Clinical cancer research, Vol.15(11), pp.3672-3679
06/01/2009
DOI: 10.1158/1078-0432.CCR-08-2343
PMCID: PMC2776721
PMID: 19458056
Abstract
Purpose: Transcriptional regulation of estrogen receptor-alpha (ERalpha) involves both epigenetic mechanisms and trans-active factors, such as TFAP2C, which induces ERalpha transcription through an AP-2 regulatory region in the ERalpha promoter. Attempts to induce endogenous ERalpha expression in ERalpha-negative breast carcinomas by forced overexpression of TFAP2C have not been successful. We hypothesize that epigenetic chromatin structure alters the activity of TFAP2C at the ERalpha promoter.
Experimental design: DNA methylation, histone acetylation, and chromatin accessibility were examined at the ERalpha promoter in a panel of breast carcinoma cell lines. TFAP2C and polymerase II binding were analyzed by chromatin immunoprecipitation. Epigenetic chromatin structure was altered using drug treatment with 5-aza-2'-deoxycytidine (AZA) and trichostatin A (TSA).
Results: The ERalpha promoter in the ERalpha-negative lines MDA-MB-231, MCF10A, and MCF7-5C show CpG island methylation, histone 3 lysine 9 deacetylation, and decreased chromatin accessibility compared with ERalpha-positive cell lines MCF7 and T47-D. Treatment with AZA/TSA increased chromatin accessibility at the ERalpha promoter and allowed TFAP2C to induce ERalpha expression in ERalpha-negative cells. Chromatin immunoprecipitation analysis showed that binding of TFAP2C to the ERalpha promoter is blocked in ERalpha-negative cells but that treatment with AZA/TSA enabled TFAP2C and polymerase II binding.
Conclusion: We conclude that the activity of TFAP2C at specific target genes depends upon epigenetic chromatin structure. Furthermore, the combination of increasing chromatin accessibility and inducing TFAP2C provides a more robust activation of the ERalpha gene in ERalpha-negative breast cancer cells.
Details
- Title: Subtitle
- Interaction of TFAP2C with the Estrogen Receptor-α Promoter Is Controlled by Chromatin Structure
- Creators
- George W Woodfield - Department of Surgery, University of Iowa, Iowa City, IowaMichael J Hitchler - Department of Radiation Oncology, University of Iowa, Iowa City, IowaYizhen Chen - Department of Surgery, University of Iowa, Iowa City, IowaFrederick E Domann - Department of Radiation Oncology, University of Iowa, Iowa City, IowaRonald J Weigel - Department of Surgery, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.15(11), pp.3672-3679
- DOI
- 10.1158/1078-0432.CCR-08-2343
- PMID
- 19458056
- PMCID
- PMC2776721
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Language
- English
- Date published
- 06/01/2009
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984025397302771
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