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Reference - PMID:35171902 - The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.

Reference summary

PubMed ID
PMID:35171902
Title
The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
Authors
Bao K, Shan CM, Chen X, Raiymbek G, Monroe JG, Fang Y, Toda T, Koutmou KS, Ragunathan K, Lu C, Berchowitz LE, Jia S
Citation
PLoS Genet 2022 Feb;18(2):e1010049
Publication year
2022
Abstract
The epigenetic landscape of a cell frequently changes in response to fluctuations in nutrient levels, but the mechanistic link is not well understood. In fission yeast, the JmjC domain protein Epe1 is critical for maintaining the heterochromatin landscape. While loss of Epe1 results in heterochromatin expansion, overexpression of Epe1 leads to defective heterochromatin. Through a genetic screen, we found that mutations in genes of the cAMP signaling pathway suppress the heterochromatin defects associated with Epe1 overexpression. We further demonstrated that the activation of Pka1, the downstream effector of cAMP signaling, is required for the efficient translation of epe1+ mRNA to maintain Epe1 overexpression. Moreover, inactivation of the cAMP-signaling pathway, either through genetic mutations or glucose deprivation, leads to the reduction of endogenous Epe1 and corresponding heterochromatin changes. These results reveal the mechanism by which the cAMP signaling pathway regulates heterochromatin landscape in fission yeast.

Annotation

GO molecular function

GO:0004674 - protein serine/threonine kinase activity

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0006993 - decreased chromatin silencing at centromere otr1R

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FYPO:0001324 - decreased protein level during vegetative growth

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FYPO:0001798 - decreased translation

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FYPO:0006992 - normal chromatin silencing at centromere otr1R

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FYPO:0003574 - normal histone H3-K14 acetylation at centromere outer repeat during vegetative growth

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FYPO:0003235 - normal histone H3-K9 methylation at centromere outer repeat during vegetative growth

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FYPO:0000833 - normal protein level during vegetative growth

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FYPO:0000091 - sensitive to thiabendazole

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Qualitative gene expression

PomGeneEx:0000019 - protein level decreased

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PomGeneEx:0000011 - RNA level increased

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Single locus phenotype

FYPO:0001324 - decreased protein level during vegetative growth

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Genotypes:

FYPO:0001798 - decreased translation

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FYPO:0006373 - increased histone H3-K9 dimethylation at heterochromatin island during vegetative growth

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