title: NF-ĸB as node for signal amplification during weaning.
abstract: 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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Fundación Investigación Hospital Clínico Valencia/INCLIVA, Universitat de Valencia, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Torres
authors.forename: Eva
authors.initials: E
authors.lastname: Serna
authors.forename: Ana
authors.initials: A
authors.lastname: Bosch
authors.forename: Rosa
authors.initials: R
authors.lastname: Zaragozá
authors.forename: Concha
authors.initials: C
authors.lastname: García
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Miralles
authors.forename: Juan
authors.initials: J
authors.lastname: Sandoval
authors.forename: Juan R
authors.initials: JR
authors.lastname: Viña
authors.forename: Elena R
authors.initials: ER
authors.lastname: García-Trevijano
mesh_terms: D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA; D050881:E1A-Associated p300 Protein