Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans.
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 devel...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-04-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011444 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850200306558697472 |
|---|---|
| author | Eillen Tecle Paaramitha Warushavithana Samuel Li Michael J Blanchard Crystal B Chhan Theresa Bui Ryan S Underwood Malina A Bakowski Emily R Troemel Vladimir Lažetić |
| author_facet | Eillen Tecle Paaramitha Warushavithana Samuel Li Michael J Blanchard Crystal B Chhan Theresa Bui Ryan S Underwood Malina A Bakowski Emily R Troemel Vladimir Lažetić |
| author_sort | Eillen Tecle |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-40413c9a3dac42d2bf33d33de836f1fd |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-40413c9a3dac42d2bf33d33de836f1fd2025-08-20T02:12:23ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-04-01214e101144410.1371/journal.pgen.1011444Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans.Eillen TeclePaaramitha WarushavithanaSamuel LiMichael J BlanchardCrystal B ChhanTheresa BuiRyan S UnderwoodMalina A BakowskiEmily R TroemelVladimir LažetićRobust 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.https://doi.org/10.1371/journal.pgen.1011444 |
| spellingShingle | Eillen Tecle Paaramitha Warushavithana Samuel Li Michael J Blanchard Crystal B Chhan Theresa Bui Ryan S Underwood Malina A Bakowski Emily R Troemel Vladimir Lažetić Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. PLoS Genetics |
| title | Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. |
| title_full | Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. |
| title_fullStr | Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. |
| title_full_unstemmed | Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. |
| title_short | Conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in Caenorhabditis elegans. |
| title_sort | conserved chromatin regulators control the transcriptional immune response to intracellular pathogens in caenorhabditis elegans |
| url | https://doi.org/10.1371/journal.pgen.1011444 |
| work_keys_str_mv | AT eillentecle conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT paaramithawarushavithana conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT samuelli conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT michaeljblanchard conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT crystalbchhan conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT theresabui conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT ryansunderwood conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT malinaabakowski conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT emilyrtroemel conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans AT vladimirlazetic conservedchromatinregulatorscontrolthetranscriptionalimmuneresponsetointracellularpathogensincaenorhabditiselegans |