Chromatin-bound IkB-alpha regulates a subset of polycomb target genes in differentiation and cancer

MARÍA CARMEN MULERO; DOLORS FERRES-MARCO; ABUL ISLAM; POL MARGALEF; MATTEO PECORARO; AGUSTÍ TOLL; NILS DRECHSEL; CRISTINA CHARNECO; SHELLY DAVIS; NICOLÁS BELLORA; FERNANDO GALLARDO; ERIKA LÓPEZ-ARRIBILLAGA; ELENA ASENSIO-JUAN; VERÓNICA RODILLA; JESSICA GONZÁLEZ; MAR IGLESIAS; VINCENT SHIH; M. MAR ALBÀ; LUCIANO DI CROCE; ALEXANDER HOFFMANN; SHIGEKI MIYAMOTO; JORDI VILLÀ-FREIXA; NURIA LÓPEZ-BIGAS; WILLIAM M. KEYES; MARÍA DOMÍNGUEZ; ANNA BIGAS; LLUÍS ESPINOSA

CANCER CELL

CELL PRESS

Lugar: United States; Año: 2013 p. 151 - 166

1535-6108

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.