Novel Roles of Caenorhabditis elegans Heterochromatin Protein HP1 and Linker Histone in the Regulation of Innate Immune Gene Expression

Abstract

Linker histone (H1) and heterochromatin protein 1 (HP1) are essential components of heterochromatin which contribute to the transcriptional repression of genes. It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1. However, the exact biological role of linker histone binding to HP1 has not been determined. Here, we investigate the function of the Caenorhabditis elegans H1 variant HIS-24 and the HP1-like proteins HPL-1 and HPL-2 in the cooperative transcriptional regulation of immune-relevant genes. We provide the first evidence that HPL-1 interacts with HIS-24 monomethylated at lysine 14 (HIS-24K14me1) and associates in vivo with promoters of genes involved in antimicrobial response. We also report an increase in overall cellular levels and alterations in the distribution of HIS-24K14me1 after infection with pathogenic bacteria. HIS-24K14me1 localization changes from being mostly nuclear to both nuclear and cytoplasmic in the intestinal cells of infected animals. Our results highlight an antimicrobial role of HIS-24K14me1 and suggest a functional link between epigenetic regulation by an HP1/H1 complex and the innate immune system in C. elegans.

ACKNOWLEDGMENTS

We thank Masoud Bahrami for integrated his-24::cfp transgene, Rania Nakad (Kiel, Germany) for the BT cultures and her help in the establishing the BT-procedure in our group, Albert Rosenberger (Göttingen, Germany) for the bioinformatics, Alejandro Vaquero (Barcelona, Spain), Hinrich Schulenburg, Katja Dierking (Kiel, Germany), Sigrid Hoyer-Fender, Mary Osborn, and Helena Miletic (Göttingen, Germany) for critically reading the manuscript, Gregor Eichele (Göttingen, Germany) for support, and Gunther Jansen (Kiel, Germany) for the help at work with PA14.

Some C. elegans strains used were obtained from the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. The his-24(ok1024) deletion mutant was provided by the C. elegans Gene Knockout Consortium, which is publicly funded. This work was supported by the German National Funding Agency (JE 505/1-3 to M.J.-B.) and the Max Planck Society (M.J.-B.).

We declare that we have no competing financial interests.