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Hurley, Jennifer M.
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Dasgupta, Arko
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Emerson, Jillian M.
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Smith, Kristina M.
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Freitag, Michael
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Zhou, Xiaoying
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Ringelberg, Carol S.
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Knabe, Nicole
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Lipzen, Anna
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Linduist, Erika A.
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Daum, Christopher G.
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Barry, Kerrie W.
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Grigoriev, Igor V.
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Galagan, James E.
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Bell-Pederson, Deborah
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Cheng, Chao
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Loros, Jennifer J.
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Dunlap, Jay C.
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| Abstract |
- Neurospora crassa has been for decades a principal model for filamentous
fungal genetics and physiology as well as for understanding
the mechanism of circadian clocks. Eukaryotic fungal and animal
clocks comprise transcription-translation-based feedback loops that
control rhythmic transcription of a substantial fraction of these transcriptomes,
yielding the changes in protein abundance that mediate
circadian regulation of physiology and metabolism: Understanding
circadian control of gene expression is key to understanding eukaryotic,
including fungal, physiology. Indeed, the isolation of clock-controlled
genes (ccgs) was pioneered in Neurospora where circadian
output begins with binding of the core circadian transcription factor
WCC to a subset of ccg promoters, including those of many transcription
factors. High temporal resolution (2-h) sampling over 48 h using
RNA sequencing (RNA-Seq) identified circadianly expressed genes in
Neurospora, revealing that from ∼10% to as much 40% of the transcriptome
can be expressed under circadian control. Functional classifications
of these genes revealed strong enrichment in pathways
involving metabolism, protein synthesis, and stress responses; in
broad terms, daytime metabolic potential favors catabolism, energy
production, and precursor assembly, whereas night activities favor
biosynthesis of cellular components and growth. Discriminative regular
expression motif elicitation (DREME) identified key promoter
motifs highly correlated with the temporal regulation of ccgs. Correlations
between ccg abundance from RNA-Seq, the degree of ccg-promoter
activation as reported by ccg-promoter-luciferase fusions, and
binding of WCC as measured by ChIP-Seq, are not strong. Therefore,
although circadian activation is critical to ccg rhythmicity, posttranscriptional
regulation plays a major role in determining rhythmicity
at the mRNA level.
- Keywords: Clock-controlled genes, Circadian, Transcription, Neurospora, RNA-Seq
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| Citation |
- Hurley, J. M., Dasgupta, A., Emerson, J. M., Zhou, X., Ringelberg, C. S., Knabe, N., ... & Dunlap, J. C. (2014). Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential. Proceedings of the National Academy of Sciences, 111(48), 16995-17002. doi:10.1073/pnas.1418963111
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| Funding Statement (additional comments about funding) |
- This work is supported by NIH-National Institute of General Medical Sciences Grants GM083336 (to J.J.L.), GM34985 and GM068087 (to J.C.D.), and DE-AC02-05CH11231 (US Department of Energy).
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