Ancestral function ofInhibitors-of-kappaB regulates Caenorhabditis elegans development

Abstract

Mammalian I kappa B proteins (I kappa Bs) exert their main function as negative regulators of NF-kappa B, a central signaling pathway controlling immunity and inflammation. An alternative chromatin role for I kappa Bs has been shown to affect stemness and cell differentiation. However, the involvement of NF-kappa B in this function has not been excluded. NFKI-1 and IKB-1 are I kappa B homologs in Caenorhabditis elegans, which lacks NF-kappa B nuclear effectors. We found that nfki-1 and ikb-1 mutants display developmental defects that phenocopy mutations in Polycomb and UTX-1 histone demethylase, suggesting a role for C. elegans I kappa Bs in chromatin regulation. Further supporting this possibility (1) we detected NFKI-1 in the nucleus of cells; (2) NFKI-1 and IKB-1 bind to histones and Polycomb proteins, (3) and associate with chromatin in vivo, and (4) mutations in nfki-1 and ikb-1 alter chromatin marks. Based on these results, we propose that ancestral I kappa B inhibitors modulate Polycomb activity at specific gene subsets with an impact on development.