Nucleotide sequence of 16-kilobase pairs of DNA 5' to the human epsilon-globin gene

Abstract

We have determined the nucleotide sequence of a 16-kilobase pair (kb) region of DNA on the 5' side of the human embryonic globin gene (epsilon). This sequence, when combined with previously published sequences, gives an uninterrupted sequence of 21 kb extending from approximately 19.5 kb upstream of the epsilon-globin gene to 0.3 kb 3' to its poly(A)-addition site. Computer-assisted analysis of this DNA reveals no large regions of self-homology but it shows the presence of seven members of the Alu family of repeated DNA, two very short members of the Kpn family of repeated DNA, one unusual direct repeat of 39 base pairs, and two potential stem and loop structures. The overall frequencies of mono- and dinucleotides within the 21 kb approximate those found in the total human genome but the distribution of (G + C)-rich regions signal many sequences of interest. The occurrences of some of the polynucleotides and polydinucleotides also differ appreciably from randomness, and the region contains several large stretches of these simple sequences. We found no evidence of strand asymmetry in the region. Homology between the nucleotide sequences of the human epsilon- and G gamma-globin genes extends only 100 base pairs 5' to the genes. One region, about 10 kb upstream of the gene, shows an apparent clustering of unusual sequence features. We discuss our sequence data in relation to the studies by others of DNAase hypersensitive sites and 5' transcription endpoints in this part of the beta-globin gene cluster.