The human histone H2A.Z gene. Sequence and regulation.

Abstract

The gene encoding the human basal histone variant H2A.Z has been cloned and sequenced. There is a single functional H2A.Z gene with several pseudogene copies. No other histone genes were found in the 3 kilobases of upstream sequence or in the 0.7 kilobase of downstream sequence. In the upstream region, there are regions of Alu sequences, located about 1375 and 2650 base pairs before the transcription start site. The amount of the H2A.Z transcript is unlinked to DNA replication; however, the amount of the H2A.Z transcript is greatly decreased as proliferating cell cultures become quiescent due in part to a decrease in the rate of transcription. Promoter sequences upstream from the H2A.Z gene have been delineated in IMR-90 cells by chloramphenicol acetyltransferase gene expression. Maximal promoter activity was found in a chloramphenicol acetyltransferase construct that contained 234 base pairs just upstream from the transcription start site. This region includes two GC boxes and three CCAAT boxes as well as a properly positioned TATA box. The organization of the human gene is similar to that of the recently characterized chicken gene (Dalton, S., Robins, A. J., Harvey, R. P., and Wells, J. R. E. (1989) Nucleic Acids Res. 17, 1745-1756). Both have four introns with identical exon-intron borders, but three of the introns in the chicken gene are much longer than those in the human. The promoter regions of the two genes have little overall homology; however, two GC boxes and one of the CCAAT boxes are conserved.