CBP Mediates NF-κB-Dependent Histone Acetylation and Estrogen Receptor Recruitment to an Estrogen Response Element in the BIRC3 Promoter
| Autor: | Jonna Frasor, Leslie A. Bembinster, Sarah C. Baumgarten, Madhumita Pradhan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Ubiquitin-Protein Ligases
Estrogen receptor Breast Neoplasms Response Elements Inhibitor of Apoptosis Proteins Histones Downregulation and upregulation Cell Line Tumor Humans CREB-binding protein Molecular Biology Transcription factor Hormone response element biology NF-kappa B Acetylation Articles Cell Biology Histone acetyltransferase CREB-Binding Protein Baculoviral IAP Repeat-Containing 3 Protein Gene Expression Regulation Neoplastic Histone Receptors Estrogen biology.protein Cancer research Female |
| Zdroj: | Molecular and Cellular Biology. 32:569-575 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.05869-11 |
| Popis: | Estrogen receptor (ER) and NF-κB are transcription factors with profound effects on breast cancer cell proliferation and survival. While many studies demonstrate that ER and NF-κB can repress each other, we previously identified a gene signature that is synergistically upregulated by these two factors in more aggressive luminal B breast tumors. Herein, we examine a novel mechanism of cross talk between ER and NF-κB that results in the upregulation of the antiapoptotic gene BIRC3 (also known as cIAP2). We demonstrate that NF-κB, acting through two response elements, is required for ER recruitment to an adjacent estrogen response element (ERE) in the BIRC3 promoter. This effect is accompanied by a major increase in NF-κB-dependent histone acetylation around the ERE. Interestingly, CBP, a histone acetyltransferase previously implicated in repressive interactions between ER and NF-κB, plays a permissive role by promoting histone acetylation and ER recruitment, as well as enhanced expression of BIRC3. These findings suggest a new gene regulatory mechanism by which inflammation and NF-κB activation can influence ER recruitment to inherently inactive ER binding sites. This fine-tuning mechanism may explain how two factors that generally repress each other's activity may work together on certain genes to promote breast cancer cell survival and tumor progression. |
| Databáze: | OpenAIRE |
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