title: CBP mediates NF-κB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Pradhan
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Baumgarten
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Bembinster
authors.forename: Jonna
authors.initials: J
authors.lastname: Frasor
mesh_terms: D000107:Acetylation; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020218:Response Elements; D044767:Ubiquitin-Protein Ligases
chemical_list: D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D011960:Receptors, Estrogen; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
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