Ancestral function of Inhibitors-of-kappaB regulatesCaenorhabditis elegansdevelopment

SummaryMammalian IκB proteins (IκBs) exert their main function as negative regulators of NF-κB, a central signaling pathway controlling immunity and inflammation. An alternative chromatin role for IκBs has been shown to affect stemness and cell differentiation. However, the involvement of NF-κB in this function has not been excluded. NFKI-1 and IKB-1 are IκB homologs inCaenorhabditis elegans, which lacks NF-κB nuclear effectors. We found thatnfki-1andikb-1mutants display developmental defects that phenocopy mutations in Polycomb and UTX-1 histone demethylase, suggesting a role forC. elegansIκBs in chromatin regulation. Further supporting this possibility(i)we detected NFKI-1 in the nucleus of cells;(ii)NFKI-1 and IKB-1 bind to histones and Polycomb proteins,(iii)and associate with chromatinin vivo, and(iv)mutations innfki-1andikb-1alter chromatin marks. Based on these results, we propose that ancestral IκB inhibitors modulate Polycomb activity at specific gene subsets with an impact on development.