Journal article
Epigenetic silencing of SOD2 by histone modifications in human breast cancer cells
Free radical biology & medicine, Vol.45(11), pp.1573-1580
2008
DOI: 10.1016/j.freeradbiomed.2008.09.005
PMCID: PMC2633123
PMID: 18845242
Abstract
Many breast cancer cells typically exhibit lower expression of manganese superoxide dismutase (MnSOD) compared to the normal cells from which they arise. This decrease can often be attributed to a defect in the transcription of
SOD2, the gene encoding MnSOD; however, the mechanism responsible for this change remains unclear. Here, we describe how altered histone modifications and a repressive chromatin structure constitute an epigenetic process to down regulate
SOD2 in human breast carcinoma cell lines. Utilizing chromatin immunoprecipitation (ChIP) we observed decreased levels of dimethyl H3K4 and acetylated H3K9 at key regulatory elements of the
SOD2 gene. Consistent with these results, we show that loss of these histone modifications creates a repressive chromatin structure at
SOD2. Transcription factor ChIP experiments revealed that this repressive chromatin structure influences the binding of SP-1, AP-1, and NFκB to
SOD2 regulatory
cis-elements
in vivo. Lastly, we show that treatment with the histone deacetylase inhibitors trichostatin A and sodium butyrate can reactivate
SOD2 expression in breast cancer cell lines. Taken together, these results indicate that epigenetic silencing of
SOD2 could be facilitated by changes in histone modifications and represent one mechanism leading to the altered expression of MnSOD observed in many breast cancers.
Details
- Title: Subtitle
- Epigenetic silencing of SOD2 by histone modifications in human breast cancer cells
- Creators
- Michael J HitchlerLarry W OberleyFrederick E Domann
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.45(11), pp.1573-1580
- DOI
- 10.1016/j.freeradbiomed.2008.09.005
- PMID
- 18845242
- PMCID
- PMC2633123
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2008
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047640402771
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