Histone gene expression is regulated by histone H2B ubiquitylation in fission yeast

Cell cycle-regulated expression of histone genes is vital for coordination of DNA replication with chromatin assembly. In yeast, histone genes are regulated by transcriptional activation in S phase and transcriptional repression in other phases of the cell cycle, although the mechanisms are poorly understood. Here we describe a role for histone H2B monoubiquitylation (H2Bub1), a histone mark that is linked to RNA polymerase II transcription elongation, in the activation of replication-dependent histone genes in the fission yeast Schizosaccharomyces pombe. Loss of H2Bub1 is also associated with a delay in S phase progression and reduced expression of the replication initiation factor Cdc18 (ortholog of Cdc6). We provide evidence that H2Bub1 impacts histone gene transcription and acts through a mechanism that involves the 3UTR. Consistent with our previous finding that H2Bub1 is functionally opposed to the elongation factor Cdk9, we also find that the effects of H2Bub1 on histone genes are suppressed by reduction in the activity of Cdk9. Our data suggest that H2Bub1 promotes cell growth by activating cell cycle-regulated genes.