title: Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer.
abstract: IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.
authors.affiliation: Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona 08003, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Mulero
authors.forename: Dolors
authors.initials: D
authors.lastname: Ferres-Marco
authors.forename: Abul
authors.initials: A
authors.lastname: Islam
authors.forename: Pol
authors.initials: P
authors.lastname: Margalef
authors.forename: Matteo
authors.initials: M
authors.lastname: Pecoraro
authors.forename: Agustí
authors.initials: A
authors.lastname: Toll
authors.forename: Nils
authors.initials: N
authors.lastname: Drechsel
authors.forename: Cristina
authors.initials: C
authors.lastname: Charneco
authors.forename: Shelly
authors.initials: S
authors.lastname: Davis
authors.forename: Nicolás
authors.initials: N
authors.lastname: Bellora
authors.forename: Fernando
authors.initials: F
authors.lastname: Gallardo
authors.forename: Erika
authors.initials: E
authors.lastname: López-Arribillaga
authors.forename: Elena
authors.initials: E
authors.lastname: Asensio-Juan
authors.forename: Verónica
authors.initials: V
authors.lastname: Rodilla
authors.forename: Jessica
authors.initials: J
authors.lastname: González
authors.forename: Mar
authors.initials: M
authors.lastname: Iglesias
authors.forename: Vincent
authors.initials: V
authors.lastname: Shih
authors.forename: M
authors.initials: M
authors.lastname: Mar Albà
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Jordi
authors.initials: J
authors.lastname: Villà-Freixa
authors.forename: Nuria
authors.initials: N
authors.lastname: López-Bigas
authors.forename: William M
authors.initials: WM
authors.lastname: Keyes
authors.forename: María
authors.initials: M
authors.lastname: Domínguez
authors.forename: Anna
authors.initials: A
authors.lastname: Bigas
authors.forename: Lluís
authors.initials: L
authors.lastname: Espinosa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002843:Chromatin; D006657:Histones; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha