Cycling off: a novel mechanism for differential cell cycle-dependent histone gene expression

The precise regulation of the replication-dependent histone genes during S phase is essential for packaging newly synthesized DNA and maintaining genome integrity. Identifying the roles of specialized factors that regulate histone biosynthesis is crucial for a comprehensive understanding of this tightly regulated process. In this issue of Genes & Development, Geisler and colleagues (doi:10.1101/gad.353837.126) investigate a previously identified repressor, Mute, and determine that it prevents the accumulation of histone mRNAs outside of S phase by antagonizing Mxc phosphorylation. They also demonstrate a novel mechanism where Mute differentially regulates histone transcript levels. Beyond the repressive mechanism of Mute, Geisler and colleagues highlight how factors can integrate multiple, distinct functions to meet the critical regulatory needs of the histone genes.