An essential role for the Ino80 chromatin remodeling complex in regulation of gene expression during cellular quiescence

Cellular quiescence is an important physiological state both in unicellular and multicellular eukaryotes. Quiescent cells are halted for proliferation and stop the cell cycle at the G(0) stage. Using fission yeast as a model organism, we have previously found that several subunits of a conserved chromatin remodeling complex, Ino80C (INOsitol requiring nucleosome remodeling factor), are required for survival in quiescence. Here, we demonstrate that Ino80C has a key function in the regulation of gene expression in G(0) cells. We show that null mutants for two Ino80C subunits, Iec1 and Ies2, a putative subunit Arp42, a null mutant for the histone variant H2A.Z, and a null mutant for the Inositol kinase Asp1 have very similar phenotypes in quiescence. These mutants show reduced transcription genome-wide and specifically fail to activate 149 quiescence genes, of which many are localized to the subtelomeric regions. Using spike in normalized ChIP-seq experiments, we show that there is a global reduction of H2A.Z levels in quiescent wild-type cells but not in iec1 increment cells and that a subtelomeric chromosome boundary element is strongly affected by Ino80C. Based on these observations, we propose a model in which Ino80C is evicting H2A.Z from chromatin in quiescent cells, thereby inactivating the subtelomeric boundary element, leading to a reorganization of the chromosome structure and activation of genes required to survive in quiescence.

Automated summary

Cellular quiescence is a vital physiological state that occurs at the G(0) stage in both single-celled and multicellular eukaryotes. The chromatin remodeling complex Ino80C has been found to play a crucial role in the survival of quiescent cells. In this study, we demonstrate that Ino80C is involved in the regulation of gene expression in G(0) cells. Null mutants for certain Ino80C subunits, the histone variant H2A.Z, and Inositol kinase Asp1 exhibit similar phenotypes in quiescence, including reduced genome-wide transcription and failure to activate quiescence genes, particularly those localized to subtelomeric regions. Our findings suggest that Ino80C evicts H2A.Z from chromatin in quiescent cells, leading to the inactivation of subtelomeric boundary element and the activation of genes necessary for survival in quiescence.