Characterization and comparison of the human and mouse Dist1/{alpha}-globin complex reveals a tightly packed multiple gene cluster containing differentially expressed transcription units

Journal Article · Tue Mar 05 00:00:00 EST 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0128· OSTI ID:459000

Kielman, M F; Smits, R; Hof, I; Bernini, L F ^[1]

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1. Leiden Univ. (Netherlands)

In this paper, we describe the detailed analysis of about 75 kb of genomic DNA flanking the 5{prime} end of the mouse {alpha}-globin region and complete the transcription map of the human region. Previously, we established the homology of the human and mouse {alpha}-globin upstream flanking regions ({alpha}UFR) and characterized in detail the mouse {alpha}-globin major regulatory element ({alpha}MRE) and the mMPG DNA repair gene. Here, we extend our analysis with the construction of a detailed restriction map, the mapping and isolation of two nonglobin genes, named mDist1 and mProx1, the distribution of 18 DNase hypersensitive sites (HSSs) in erythroid and fibroblast cells, and the analysis of the mDist1, mMPG, and mProx1 expression levels in several adult tissues and during fetal development. In addition, the hDist1 gene is exactly localized 1.9 kb from the hMPG gene. The mapping results show that the Dist1, MPG, and Prox1 genes, together with the {alpha}-globin genes and the {alpha}MRE, form a tightly packed multiple gene cluster that is 50% more compact in mouse than in human. The expression results show that each of the genes present in this locus displays a characteristic expression pattern in adult tissues and during fetal development. The 18 DNase HSSs observed were scattered over this region. Interestingly, all the erythroid-sensitive HSSs were associated with the Prox1 transcription unit, whereas the only two pairs of fibroblast-sensitive HSSs present in this locus were located in the promoter regions of the mProx1 and mDist1/mMPG genes. The possible role of the erythroid- and fibroblast-sensitive HSSs present in this locus were located in the promoter regions of the mProx1 and mDist1/mMPG genes. The possible role of the erythroid- and fibroblast-sensitive sites in the regulation of the mouse {alpha}-globin and nonglobin gene expression is discussed. 38 refs., 3 figs.

• OSTI ID: 459000
• Journal Information: Genomics, Vol. 32, Issue 3; Other Information: PBD: 5 Mar 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
HUMAN CHROMOSOMES
GENETIC MAPPING
HUMAN CHROMOSOME 16
MICE
COMPARATIVE EVALUATIONS
ONTOGENESIS
GENES
GENE REGULATION
TRANSCRIPTION
TISSUE DISTRIBUTION
BIOLOGICAL EVOLUTION
STRUCTURE-ACTIVITY RELATIONSHIPS
GENE MUTATIONS
MAN
DNA
DNA REPAIR
POLYMERASE CHAIN REACTION
TELOMERES
COSMIDS
DNA-CLONING