Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development

Brena, David; Bertran, Joan; Porta de la Riva, Montserrat; Guillén, Yolanda; Cornes Maragliano, Eric, 1987-; Kukhtar, Dmytro; Campos-Vicens, Lluís; Fernández, Lierni; Pecharroman, Irene; García-López, Albert; Islam, Abul, 1978-; Marruecos, Laura; Bigas Salvans, Anna; Cerón Madrigal, Julián; Espinosa Blay, Lluís

doi:http://dx.doi.org/10.1038/s41598-020-73146-5

Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development

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Brena D, Bertran J, Porta-de-la-Riva M, Guillén Y, Cornes E, Kukhtar D, et al. Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development. Sci Rep. 2020 Sep 30; 10(1): 16153. DOI: 10.1038/s41598-020-73146-5

Abstract

Mammalian 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 in Caenorhabditis elegans, which lacks NF-κB 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 IκBs 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 IκB inhibitors modulate Polycomb activity at specific gene subsets with an impact on development.