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Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development

Coordinating the balance between development and stress responses is critical for organismal survival. However, the cellular signaling controlling this mechanism is not well understood. In Caenorhabditis elegans, it has been hypothesized that a genetic network regulated by NIPI-3/Tibbles may control...

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Autores principales: Malinow, Rose Aria, Zhu, Ming, Jin, Yishi, Kim, Kyung Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525577/
https://www.ncbi.nlm.nih.gov/pubmed/36180459
http://dx.doi.org/10.1038/s41598-022-20361-x
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author Malinow, Rose Aria
Zhu, Ming
Jin, Yishi
Kim, Kyung Won
author_facet Malinow, Rose Aria
Zhu, Ming
Jin, Yishi
Kim, Kyung Won
author_sort Malinow, Rose Aria
collection PubMed
description Coordinating the balance between development and stress responses is critical for organismal survival. However, the cellular signaling controlling this mechanism is not well understood. In Caenorhabditis elegans, it has been hypothesized that a genetic network regulated by NIPI-3/Tibbles may control the balance between animal development and immune response. Using a nipi-3(0) lethality suppressor screen in C. elegans, we reveal a novel role for N-terminal acetyltransferase C complex natc-1/2/3 and histone deacetylase hda-4, in the control of animal development. These signaling proteins act, at least in part, through a PMK-1 p38 MAP kinase pathway (TIR-1–NSY-1–SEK-1–PMK-1), which plays a critical role in the innate immunity against infection. Additionally, using a transcriptional reporter of SEK-1, a signaling molecule within this p38 MAP kinase system that acts directly downstream of C/EBP bZip transcription factor CEBP-1, we find unexpected positive control of sek-1 transcription by SEK-1 along with several other p38 MAP kinase pathway components. Together, these data demonstrate a role for NIPI-3 regulators in animal development, operating, at least in part through a PMK-1 p38 MAPK pathway. Because the C. elegans p38 MAP kinase pathway is well known for its role in cellular stress responses, the novel biological components and mechanisms pertaining to development identified here may also contribute to the balance between stress response and development.
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spelling pubmed-95255772022-10-02 Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development Malinow, Rose Aria Zhu, Ming Jin, Yishi Kim, Kyung Won Sci Rep Article Coordinating the balance between development and stress responses is critical for organismal survival. However, the cellular signaling controlling this mechanism is not well understood. In Caenorhabditis elegans, it has been hypothesized that a genetic network regulated by NIPI-3/Tibbles may control the balance between animal development and immune response. Using a nipi-3(0) lethality suppressor screen in C. elegans, we reveal a novel role for N-terminal acetyltransferase C complex natc-1/2/3 and histone deacetylase hda-4, in the control of animal development. These signaling proteins act, at least in part, through a PMK-1 p38 MAP kinase pathway (TIR-1–NSY-1–SEK-1–PMK-1), which plays a critical role in the innate immunity against infection. Additionally, using a transcriptional reporter of SEK-1, a signaling molecule within this p38 MAP kinase system that acts directly downstream of C/EBP bZip transcription factor CEBP-1, we find unexpected positive control of sek-1 transcription by SEK-1 along with several other p38 MAP kinase pathway components. Together, these data demonstrate a role for NIPI-3 regulators in animal development, operating, at least in part through a PMK-1 p38 MAPK pathway. Because the C. elegans p38 MAP kinase pathway is well known for its role in cellular stress responses, the novel biological components and mechanisms pertaining to development identified here may also contribute to the balance between stress response and development. Nature Publishing Group UK 2022-09-30 /pmc/articles/PMC9525577/ /pubmed/36180459 http://dx.doi.org/10.1038/s41598-022-20361-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Malinow, Rose Aria
Zhu, Ming
Jin, Yishi
Kim, Kyung Won
Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title_full Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title_fullStr Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title_full_unstemmed Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title_short Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development
title_sort forward genetic screening identifies novel roles for n-terminal acetyltransferase c and histone deacetylase in c. elegans development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525577/
https://www.ncbi.nlm.nih.gov/pubmed/36180459
http://dx.doi.org/10.1038/s41598-022-20361-x
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