The human H2A and H2B histone gene complement

Sequences and expression patterns of newly isolated human histone H2A and H 2B genes and the respective proteins were compared with previously isolated human H2A and H2B genes and proteins. Altogether, 15 human H2A genes and 1 7 human H2B genes have been identified. 14 of these are organized as H2A/H2 B gene pairs, while one H2A gene and three H2B genes are solitary genes. Tw o H2A genes and two H2B genes turned out to be pseudogenes. The 13 H2A gene s code for at least 6 different amino acid sequences, and the 15 H2B genes encode 11 different H2B isoforms. Each H2A/H2B gene pair is controlled by a divergent promoter spanning 300 to 330 nucleotides between the coding regi ons of the two genes. The highly conserved divergent H2A/H2B promoters can be classified in two groups based on the patterns of consensus sequence ele ments. Group I promoters contain a TATA box for each gene, two Oct-1 factor binding sites, and three CCAAT boxes. Group II promoters contain the same elements as group I promoters and an additional CCAAT box, a binding motif for E2F and adjacent a highly conserved octanucleotide (CACAGCTT) that has not been described so far. Five of the 6 gene pairs and 4 solitary genes wi th group I promoters are localized in the large histone gene cluster at 6p2 1.3-6p22, and one gene pair is located at 1q21. All group II promoter assoc iated genes are contained within the histone gene subcluster at D6S105, whi ch is located at a distance of about 2 Mb from the major subcluster at 6p21 .3-6p22 containing histone genes with group I promoters. Almost all group I I H2A genes encode identical amino acid sequences, whereas group I H2A gene products vary at several positions. Using human cell lines, we have analyz ed the expression patterns of functional human H2A/H2B gene pairs organized within the two histone gene clusters on the short arm of chromosome 6. The genes show varying expression patterns in different tumor cell lines.