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Chromatin-bound I?B? regulates a subset of polycomb target genes in differentiation and cancer.

ABSTRACT: I?B proteins are the primary inhibitors of NF-?B. Here, we demonstrate that sumoylated and phosphorylated I?B? accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound I?B? modulates Polycomb recruitment and imparts their competence to be activated by TNF?. Mutations in the Drosophila I?B? gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-?B. Oncogenic transformation of keratinocytes results in cytoplasmic I?B? translocation associated with a massive activation of Hox. Accumulation of cytoplasmic I?B? was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.

SUBMITTER: Mulero MC 

PROVIDER: S-EPMC3962677 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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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.  ...[more]

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