Differential regulation of repeated histone genes during the fission yeast cell cycle

The histone genes are highly reiterated in a wide range of eukaryotic genomes. The fission yeast, Schizosaccharomyces pombe, has three pairs of histone H3-H4 genes: hht1+-hhf1+, hht2+-hhf2+ and hht3+-hhf3+. While the deduced amino acid sequences are identical, it remains unknown whether transcriptional regulation differs among the three pairs. Here, we report the transcriptional properties of each H3-H4 gene pair during the cell cycle. The levels of transcripts of hht1+-hhf1+ and hht3+-hhf3+ pairs and hhf2+ are increased at S-phase, while that of hht2+ remains constant throughout the cell cycle. We showed that the GATA-type transcription factor, Ams2, binds to the promoter regions of core histone genes in an AACCCT-box-dependent manner and is required for activation of S-phase-specific transcription. Furthermore, we found that Ams2-depletion stimulates feedback regulation of histone transcripts, mainly up-regulating the basal levels of hht2+-hhf2+ transcription, which are normally down-regulated by Hip1 and Slm9, homologs of the human histone chaperone, HIRA. These observations provide insight into the molecular mechanisms of differential regulation of transcripts from repeated histone genes in the fission yeast.