CBP/p300 and SIRT1 Are Involved in Transcriptional Regulation of S-Phase Specific Histone Genes

BACKGROUND: Histones constitute a type of essential nuclear proteins important for chromatin structure and functions. The expression of major histones is strictly confined to the S phase of a cell cycle and tightly coupled to DNA replication. METHODOLOGY/PRINCIPAL FINDINGS: With RT-qPCR and ChIP assays, we investigated transcriptional regulation of the S-phase specific histone genes and found that the acetylation level of histones on core histone gene promoters fluctuated during cell cycle in a pattern similar to RNA polymerase II association. Further, we showed that CBP/p300 and SIRT1 were recruited to histone gene promoters in an NPAT-dependent manner, knockdown of which affected histone acetylation on histone gene promoters and histone gene transcription. SIGNIFICANCE: These observations contribute to further understanding of the mechanism by which the expression of canonical histone genes is regulated, and also implicate a link between histone expression and DNA damage repair and cell metabolism.