Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. PLoS Genet 2025 Apr;21(4):e1011444
Date
04/07/2025Pubmed ID
40193347Pubmed Central ID
PMC11975079DOI
10.1371/journal.pgen.1011444Scopus ID
2-s2.0-105002142577 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
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.
Author List
Tecle E, Warushavithana P, Li S, Blanchard MJ, Chhan CB, Bui T, Underwood RS, Bakowski MA, Troemel ER, Lažetić VAuthor
Eillen Tecle PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCaenorhabditis elegans
Caenorhabditis elegans Proteins
Chromatin
Chromatin Assembly and Disassembly
Gene Expression Regulation
Immunity, Innate
Mutation
Repressor Proteins
Transcription Factors
