S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress
Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function h...
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eLife Sciences Publications Ltd
2023-02-01
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Online Access: | https://elifesciences.org/articles/79511 |
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author | Adwait A Godbole Sneha Gopalan Thien-Kim Nguyen Alexander L Munden Dominique S Lui Matthew J Fanelli Paula Vo Caroline A Lewis Jessica B Spinelli Thomas G Fazzio Amy K Walker |
author_facet | Adwait A Godbole Sneha Gopalan Thien-Kim Nguyen Alexander L Munden Dominique S Lui Matthew J Fanelli Paula Vo Caroline A Lewis Jessica B Spinelli Thomas G Fazzio Amy K Walker |
author_sort | Adwait A Godbole |
collection | DOAJ |
description | Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1, however, sams-1 cannot compensate for sams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1 CC function to phenotypes in aging and stress. |
first_indexed | 2024-04-10T05:56:17Z |
format | Article |
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institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-10T05:56:17Z |
publishDate | 2023-02-01 |
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spelling | doaj.art-8ef70ae4ac0b4ed6b07168ee56561b9a2023-03-03T16:26:15ZengeLife Sciences Publications LtdeLife2050-084X2023-02-011210.7554/eLife.79511S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stressAdwait A Godbole0Sneha Gopalan1Thien-Kim Nguyen2Alexander L Munden3Dominique S Lui4Matthew J Fanelli5Paula Vo6Caroline A Lewis7Jessica B Spinelli8Thomas G Fazzio9https://orcid.org/0000-0002-0353-7466Amy K Walker10https://orcid.org/0000-0003-1899-8916Program in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesCancer Center, UMASS Chan Medical School, Worcester, United States; Department of Molecular, Cell, and Cancer Biology, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United States; Cancer Center, UMASS Chan Medical School, Worcester, United StatesCancer Center, UMASS Chan Medical School, Worcester, United States; Department of Molecular, Cell, and Cancer Biology, UMASS Chan Medical School, Worcester, United StatesProgram in Molecular Medicine, UMASS Chan Medical School, Worcester, United States; Department of Molecular, Cell, and Cancer Biology, UMASS Chan Medical School, Worcester, United StatesMethylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1, however, sams-1 cannot compensate for sams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1 CC function to phenotypes in aging and stress.https://elifesciences.org/articles/79511methyl donor metabolismH3K4 methylationheat shock |
spellingShingle | Adwait A Godbole Sneha Gopalan Thien-Kim Nguyen Alexander L Munden Dominique S Lui Matthew J Fanelli Paula Vo Caroline A Lewis Jessica B Spinelli Thomas G Fazzio Amy K Walker S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress eLife methyl donor metabolism H3K4 methylation heat shock |
title | S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress |
title_full | S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress |
title_fullStr | S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress |
title_full_unstemmed | S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress |
title_short | S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress |
title_sort | s adenosylmethionine synthases specify distinct h3k4me3 populations and gene expression patterns during heat stress |
topic | methyl donor metabolism H3K4 methylation heat shock |
url | https://elifesciences.org/articles/79511 |
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