CBP mediates NF-?B-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter.

ABSTRACT: Estrogen receptor (ER) and NF-?B are transcription factors with profound effects on breast cancer cell proliferation and survival. While many studies demonstrate that ER and NF-?B 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-?B that results in the upregulation of the antiapoptotic gene BIRC3 (also known as cIAP2). We demonstrate that NF-?B, 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-?B-dependent histone acetylation around the ERE. Interestingly, CBP, a histone acetyltransferase previously implicated in repressive interactions between ER and NF-?B, 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-?B 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.

SUBMITTER: Pradhan M 

PROVIDER: S-EPMC3255764 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature