The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.

The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic funct...

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Autores principales:	David W Johnson, Jesse R Llop, Sara F Farrell, Jie Yuan, Lindsay R Stolzenburg, Andrew V Samuelson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/9744c6b641514d79967098ddb30f86d4
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spelling	oai:doaj.org-article:9744c6b641514d79967098ddb30f86d42021-11-18T06:20:56ZThe Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.1553-73901553-740410.1371/journal.pgen.1004278https://doaj.org/article/9744c6b641514d79967098ddb30f86d42014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24699255/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic functions in transcriptional control: the Myc-Mondo:Mlx transcriptional activation complex and the Mad:Max transcriptional repression complex. In C. elegans, Mondo, Mlx, Mad, and Max are encoded by mml-1, mxl-2, mdl-1, and mxl-1, respectively. Here we show a similar antagonistic role for the C. elegans Myc-Mondo and Mad complexes in longevity control. Loss of mml-1 or mxl-2 shortens C. elegans lifespan. In contrast, loss of mdl-1 or mxl-1 increases longevity, dependent upon MML-1:MXL-2. The MML-1:MXL-2 and MDL-1:MXL-1 complexes function in both the insulin signaling and dietary restriction pathways. Furthermore, decreased insulin-like/IGF-1 signaling (ILS) or conditions of dietary restriction increase the accumulation of MML-1, consistent with the notion that the Myc family members function as sensors of metabolic status. Additionally, we find that Myc family members are regulated by distinct mechanisms, which would allow for integrated control of gene expression from diverse signals of metabolic status. We compared putative target genes based on ChIP-sequencing data in the modENCODE project and found significant overlap in genomic DNA binding between the major effectors of ILS (DAF-16/FoxO), DR (PHA-4/FoxA), and Myc family (MDL-1/Mad/Mxd) at common target genes, which suggests that diverse signals of metabolic status converge on overlapping transcriptional programs that influence aging. Consistent with this, there is over-enrichment at these common targets for genes that function in lifespan, stress response, and carbohydrate metabolism. Additionally, we find that Myc family members are also involved in stress response and the maintenance of protein homeostasis. Collectively, these findings indicate that Myc family members integrate diverse signals of metabolic status, to coordinate overlapping metabolic and cytoprotective transcriptional programs that determine the progression of aging.David W JohnsonJesse R LlopSara F FarrellJie YuanLindsay R StolzenburgAndrew V SamuelsonPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 10, Iss 4, p e1004278 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 David W Johnson Jesse R Llop Sara F Farrell Jie Yuan Lindsay R Stolzenburg Andrew V Samuelson The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
description	The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic functions in transcriptional control: the Myc-Mondo:Mlx transcriptional activation complex and the Mad:Max transcriptional repression complex. In C. elegans, Mondo, Mlx, Mad, and Max are encoded by mml-1, mxl-2, mdl-1, and mxl-1, respectively. Here we show a similar antagonistic role for the C. elegans Myc-Mondo and Mad complexes in longevity control. Loss of mml-1 or mxl-2 shortens C. elegans lifespan. In contrast, loss of mdl-1 or mxl-1 increases longevity, dependent upon MML-1:MXL-2. The MML-1:MXL-2 and MDL-1:MXL-1 complexes function in both the insulin signaling and dietary restriction pathways. Furthermore, decreased insulin-like/IGF-1 signaling (ILS) or conditions of dietary restriction increase the accumulation of MML-1, consistent with the notion that the Myc family members function as sensors of metabolic status. Additionally, we find that Myc family members are regulated by distinct mechanisms, which would allow for integrated control of gene expression from diverse signals of metabolic status. We compared putative target genes based on ChIP-sequencing data in the modENCODE project and found significant overlap in genomic DNA binding between the major effectors of ILS (DAF-16/FoxO), DR (PHA-4/FoxA), and Myc family (MDL-1/Mad/Mxd) at common target genes, which suggests that diverse signals of metabolic status converge on overlapping transcriptional programs that influence aging. Consistent with this, there is over-enrichment at these common targets for genes that function in lifespan, stress response, and carbohydrate metabolism. Additionally, we find that Myc family members are also involved in stress response and the maintenance of protein homeostasis. Collectively, these findings indicate that Myc family members integrate diverse signals of metabolic status, to coordinate overlapping metabolic and cytoprotective transcriptional programs that determine the progression of aging.
format	article
author	David W Johnson Jesse R Llop Sara F Farrell Jie Yuan Lindsay R Stolzenburg Andrew V Samuelson
author_facet	David W Johnson Jesse R Llop Sara F Farrell Jie Yuan Lindsay R Stolzenburg Andrew V Samuelson
author_sort	David W Johnson
title	The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
title_short	The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
title_full	The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
title_fullStr	The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
title_full_unstemmed	The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.
title_sort	caenorhabditis elegans myc-mondo/mad complexes integrate diverse longevity signals.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9744c6b641514d79967098ddb30f86d4
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The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals.

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