| Abstrakt: |
In this paper, we describe the detailed analysis of about 75 kb of genomic DNA flanking the 5′ end of the mouse α-globinregion and complete the transcription map of the human region. Previously, we established the homology of the human and mouse α-globinupstream flanking regions (αUFR) and characterized in detail the mouse α-globin major regulatory element (αMRE) and themMPGDNA repair gene. Here, we extend our analysis with the construction of a detailed restriction map, the mapping and isolation of twononglobingenes, namedmDist1andmProx1,the distribution of 18 DNase hypersensitive sites (HSSs) in erythroid and fibroblast cells, and the analysis of themDist1, mMPG,andmProx1expression levels in several adult tissues and during fetal development. In addition, thehDist1gene is exactly localized 1.9 kb from thehMPGgene. The mapping results show that theDist1, MPG,andProx1genes, together with the α-globingenes and the αMRE, 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 theProx1transcription unit, whereas the only two pairs of fibroblast-sensitive HSSs present in this locus were located in the promoter regions of themProx1andmDist1/mMPGgenes. The possible role of the erythroid- and fibroblast-sensitive sites in the regulation of the mouse α-globinandnonglobingene expression is discussed. The characterization of the mouse αUFR identifies most, if not all, of the structural elements possibly involved in the regulation ofmα-globingene expression and sheds light on the organization and evolution of the telomere-associated, GC-rich isochore family H3. |
Full Text from ScienceDirect