, Volume 4, Issue 6, pp 314-323

Homology of a 130-kb region enclosing the α-globin gene cluster, the α-locus controlling region, and two non-globin genes in human and mouse

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Abstract

The human α-globin gene cluster (30 kb) is embedded in a GC-rich isochore very close to the telomere of Chromosome (Chr) 16p. The α-Locus Controlling Region (α-LCR) is located upstream of the adult α-globin genes and has been shown to be essential for their expression. In this study we have been looking for expressed genes in the region upstream of the α-globin cluster to understand the role of the LCR-like element in the expression and replication timing of flanking gene clusters. We show that the upstream α-globin region is conserved over a 75-kb range and includes at least two oppositely transcribed non-globin genes, here referred to as Mid1 and Dist1. Complementary DNA sequences of 250 bp and 2.5 kb from Mid1 (coordinate-68) and Dist1 (coordinate-90 to-99), respectively, were isolated from human and mouse. The deduced partial amino acid sequences of these cDNAs are 81% and 95% identical for the Mid1 and Dist1 gene respectively. We have cloned a mouse cosmid “contig” which includes Dist1, Mid1, and the entire murine α-globin cluster. The murine homolog of the α-LCR was mapped upstream of the mouse globin genes at approximately the same position as in the human locus. Our results indicate that, in mouse and human, the α-globin loci and their flanking sequences are homologous over a range of at least 130 kb. The structural homology of this region in both mammals suggests also a functional one and indicates the mouse as a potential model for studying the role of the α-LCR controlling element in the regulation of expression and replication timing of the flanking gene clusters.

The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession numbers M99623, M99624, M99625, and M99626.