Open AccessNF-ĸB as Node for Signal Amplification During Weaning
Author(s) -
Luís Torres,
Eva Serna,
Ana Bosch,
Rosa Zaragozá,
Carlos J. Gómez García,
Vicente J. Miralles,
Juan Sandoval,
Juan R. Viña,
Elena R. Garcı́a-Trevijano
Publication year - 2011
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000335797
Subject(s) - biology , gene , involution (esoterism) , transcription factor , mammary gland , activator (genetics) , promoter , nf κb , microbiology and biotechnology , gene expression , cancer research , signal transduction , breast cancer , medicine , genetics , cancer , neuroscience , consciousness
Post-lactational involution has been reported to share common features with breast tumor development. A deep characterization of the signaling triggered after weaning would help to unveil the complex relationship between involution and breast cancer. NF-κB, a crucial factor in the involuting gland, might be an important regulatory node for signal amplification after weaning; however there is limited information about the identity of NF-κB-target genes and the molecular mechanisms leading to the selection of genes involved in a particular biological process. We identified 4532 target genes in mammary gland at 48h weaning, by genome-wide analysis of regions bound by RelA(p65)-NF-κB in vivo. It was found that among total RelA(p65)-NF-κB-enriched genes, only 268 bound the trans-activating complex p65/p300. Our results suggest that the latter represents a major complex preferentially involved in the modulation of the inflammatory response at 48 h of mammary gland involution. A genome-wide factor location analysis revealed that p65-binding had a heterogeneous distribution while the complex of p65 and its co-activator p300 were mainly bound to proximal promoters near transcription start sites. Moreover, our computational analysis predicts the existence of cooperating elements on RelA-NF-κB/p300-enriched genes that could explain preferential binding and modulation of gene expression during mammary gland involution.