Department of Biological Sciences, Columbia University, New York, New York, United States of America.
Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York, United States of America.
PLoS Genet. 2022 Feb 16;18(2):e1010049. doi: 10.1371/journal.pgen.1010049. eCollection 2022 Feb.
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.
细胞的表观遗传景观经常会因营养水平的波动而发生变化，但其中的机制联系还不是很清楚。在裂殖酵母中，JmjC 结构域蛋白 Epe1 对于维持异染色质景观至关重要。虽然 Epe1 的缺失会导致异染色质扩张，但 Epe1 的过表达会导致异染色质缺陷。通过遗传筛选，我们发现 cAMP 信号通路基因的突变可以抑制与 Epe1 过表达相关的异染色质缺陷。我们进一步证明，cAMP 信号通路的下游效应物 Pka1 的激活对于有效地翻译 epe1+mRNA 以维持 Epe1 过表达是必需的。此外，无论是通过基因突变还是葡萄糖剥夺，cAMP 信号通路的失活都会导致内源性 Epe1 的减少和相应的异染色质变化。这些结果揭示了 cAMP 信号通路在裂殖酵母中调节异染色质景观的机制。
