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.