The cAMP signaling pathway regulates Epe1 protein levels and heterochromatin assembly.
Kehan BaoChun-Min ShanXiao ChenGulzhan RaiymbekJeremy G MonroeYimeng FangTakenori TodaKristin D KoutmouKaushik RagunathanAndrew O M WilkieLuke E BerchowitzSongtao JiaPublished in: PLoS genetics (2022)
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.
Keyphrases
- signaling pathway
- binding protein
- pi k akt
- single cell
- genome wide
- cell proliferation
- epithelial mesenchymal transition
- protein kinase
- transcription factor
- dna methylation
- gene expression
- stem cells
- protein protein
- high throughput
- copy number
- regulatory t cells
- metabolic syndrome
- adipose tissue
- saccharomyces cerevisiae
- immune response
- endoplasmic reticulum stress
- type iii