Yeast two-hybrid analysis of PALS-20 and PALS-25.

Robust transcriptional responses are critical for defense against infection. However, unrestrained immune responses can cause negative impacts such as damaging inflammation and slowed development. Here, we find that a class of transcriptional regulators previously associated with regulation of development in Caenorhabditis elegans, is also involved in repressing immune responses. Specifically, through forward genetics, we find that loss of lin-15B leads to constitutive expression of Intracellular Pathogen Response (IPR) genes. lin-15B encodes a transcriptional repressor with a conserved THAP domain that is associated with the DRM chromatin remodeling complex that regulates C. elegans development. We show that lin-15B mutants have increased resistance to natural intracellular pathogens, and the induction of IPR genes in lin-15B mutants relies on the MES-4 histone methyltransferase. We extend our analyses to other DRM and NuRD chromatin remodeling factors, as well as SUMOylation histone modifiers, showing that a broad range of chromatin-related factors can repress IPR gene expression. Altogether these findings suggest that conserved chromatin regulators may facilitate development in part by repressing damaging immune responses against intracellular pathogens.