CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter.
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Pradhan M, Baumgarten SC, Bembinster LA, Frasor J
CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter.
Mol Cell Biol. 2012 Jan;32(2):569-75. doi: 10.1128/MCB.05869-11. Epub 2011 Nov 14.
- PubMed ID
- 22083956 [ View in PubMed]
- Abstract
Estrogen receptor (ER) and NF-kappaB are transcription factors with profound effects on breast cancer cell proliferation and survival. While many studies demonstrate that ER and NF-kappaB 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-kappaB that results in the upregulation of the antiapoptotic gene BIRC3 (also known as cIAP2). We demonstrate that NF-kappaB, 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-kappaB-dependent histone acetylation around the ERE. Interestingly, CBP, a histone acetyltransferase previously implicated in repressive interactions between ER and NF-kappaB, 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-kappaB 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.