The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.

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 heterochromat...

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Main Authors: Kehan Bao, Chun-Min Shan, Xiao Chen, Gulzhan Raiymbek, Jeremy G Monroe, Yimeng Fang, Takenori Toda, Kristin S Koutmou, Kaushik Ragunathan, Chao Lu, Luke E Berchowitz, Songtao Jia
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-02-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1010049
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author Kehan Bao
Chun-Min Shan
Xiao Chen
Gulzhan Raiymbek
Jeremy G Monroe
Yimeng Fang
Takenori Toda
Kristin S Koutmou
Kaushik Ragunathan
Chao Lu
Luke E Berchowitz
Songtao Jia
author_facet Kehan Bao
Chun-Min Shan
Xiao Chen
Gulzhan Raiymbek
Jeremy G Monroe
Yimeng Fang
Takenori Toda
Kristin S Koutmou
Kaushik Ragunathan
Chao Lu
Luke E Berchowitz
Songtao Jia
author_sort Kehan Bao
collection DOAJ
description 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.
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spelling doaj.art-1c262db5a8464ee0a433fff8500f564e2022-12-22T03:28:28ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-02-01182e101004910.1371/journal.pgen.1010049The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.Kehan BaoChun-Min ShanXiao ChenGulzhan RaiymbekJeremy G MonroeYimeng FangTakenori TodaKristin S KoutmouKaushik RagunathanChao LuLuke E BerchowitzSongtao JiaThe 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.https://doi.org/10.1371/journal.pgen.1010049
spellingShingle Kehan Bao
Chun-Min Shan
Xiao Chen
Gulzhan Raiymbek
Jeremy G Monroe
Yimeng Fang
Takenori Toda
Kristin S Koutmou
Kaushik Ragunathan
Chao Lu
Luke E Berchowitz
Songtao Jia
The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
PLoS Genetics
title The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
title_full The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
title_fullStr The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
title_full_unstemmed The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
title_short The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
title_sort camp signaling pathway regulates epe1 protein levels and heterochromatin assembly
url https://doi.org/10.1371/journal.pgen.1010049
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