Transcriptional regulation of the human replacement histone gene H3.3B

In contrast to the cell-cycle-dependent histone genes, replacement histone genes are transcribed independently of DNA replication and their expression is upregulated during differentiation. We have investigated the transcriptional regulation of the recently characterized human replacement histone gene H3.3B. Using reporter gene assays of promoter-luciferase gene-constructs, we show that promoter activity largely depends on an intact Oct and CRE/TRE element within the proximal 145 bp of the promoter. DNase I footprinting revealed binding of proteins to a 40-bp region covering these two elements. Band shift experiments identified binding proteins as Oct-1 and factors of the CREB/ATF and AP-1 family, respectively. The unexpected transcriptional regulation of this replacement histone gene is discussed.