10.5061/DRYAD.PJ0P3
Johnson, David W.
University of Rochester
Llop, Jesse R.
University of Rochester
Farrell, Sara F.
University of Rochester
Yuan, Jie
Rochester Institute of Technology
Stolzenburg, Lindsay R.
Northwestern University
Samuelson, Andrew Vaughn
University of Rochester
Data from: The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate
diverse longevity signals
Dryad
dataset
2015
mondo
max
caloric restriction
Transcription factors
mad
Caenorhabditis elegans
Insulin signaling
Myc
nutrient sensing
mlx
Dietary restriction
genetics of aging
2015-03-06T00:00:00Z
2015-03-06T00:00:00Z
en
https://doi.org/10.1371/journal.pgen.1004278
118603 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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.
Raw Data of Mortality Observations of Replica Set ExperimentsDryad File.xlsx