Chromatin-bound IκB-alpha regulates a subset of polycomb target genes in differentiation and cancer
Chromatin-bound IκB-alpha regulates a subset of polycomb target genes in differentiation and cancer
Citació
- Mulero MC, Ferres-Marco D, Islam A, Margalef P, Pecoraro M, Toll A et al. Chromatin-bound IκB-alpha regulates a subset of polycomb target genes in differentiation and cancer. Cancer Cell. 2013; 24(2): 151-166. DOI 10.1016/j.ccr.2013.06.003
Enllaç permanent
Descripció
Resum
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 TNF-alpha. 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.