Heat Stress-induced Activation of MAPK Pathway Attenuates Atf1-dependent Epigenetic Inheritance of Heterochromatin in Fission Yeast

Abstract

ABSTRACTEukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeastSchizosaccharomyces pombe, heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type (mat) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at thematlocus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of MAPK signaling disrupts epigenetic maintenance of heterochromatin at thematlocus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6HP1, resulting in lower site-specific Swi6HP1enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6HP1to themat3M-flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at thematlocus.