ISSN:
1432-1777
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00357090
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