Caughey G H, Schaumberg T H, Zerweck E H, Butterfield J H, Hanson R D, Silverman G A, Ley T J
Cardiovascular Research Institute, University of California, San Francisco 94143.
Genomics. 1993 Mar;15(3):614-20. doi: 10.1006/geno.1993.1115.
Genes encoding T-cell-receptor alpha/delta chains, neutrophil cathepsin G, and lymphocyte CGL/granzymes are closely linked on chromosomal band 14q11.2. The current work identifies the human mast cell chymase gene (CMA1) as the fourth protease in this cluster and maps the gene to within 150 kb of the cathepsin G gene. The gene order is centromere-T cell receptor alpha/delta-CGL-1/granzyme B-CGL-2/granzyme H-cathepsin G-chymase. Chymase and cathepsin G genes are shown to be cotranscribed in the human mast cell line HMC-1 and in U-937 cells. Other cells transcribe cathepsin G or CGL/granzyme genes, but not chymase genes, suggesting a capacity for independent regulation. Comparison of the 5' flank of the chymase gene with those of cathepsin G and CGL/granzymes reveals little overall homology. Only short regions of the 5' flanks of the human and murine chymase gene sequenced to date are similar, suggesting that they are more distantly related than human and rodent CGL-1/granzyme B, the flanks of which are highly homologous. The expression patterns and clustering of genes provide possible clues to the presence of locus control regions that orchestrate lineage-restricted expression of leukocyte and mast cell proteases.
编码T细胞受体α/δ链、中性粒细胞组织蛋白酶G和淋巴细胞CGL/颗粒酶的基因在染色体带14q11.2上紧密连锁。当前研究确定人类肥大细胞糜酶基因（CMA1）是该基因簇中的第四个蛋白酶基因，并将该基因定位在组织蛋白酶G基因的150 kb范围内。基因顺序为着丝粒-T细胞受体α/δ-CGL-1/颗粒酶B-CGL-2/颗粒酶H-组织蛋白酶G-糜酶。研究表明，糜酶和组织蛋白酶G基因在人类肥大细胞系HMC-1和U-937细胞中共同转录。其他细胞转录组织蛋白酶G或CGL/颗粒酶基因，但不转录糜酶基因，这表明它们具有独立调控的能力。将糜酶基因的5'侧翼与组织蛋白酶G和CGL/颗粒酶的5'侧翼进行比较，发现总体同源性较低。迄今为止测序的人类和小鼠糜酶基因5'侧翼只有短区域相似，这表明它们的亲缘关系比人类和啮齿动物的CGL-1/颗粒酶B更远，后者的侧翼具有高度同源性。基因的表达模式和聚类为协调白细胞和肥大细胞蛋白酶谱系限制性表达的基因座控制区域的存在提供了可能的线索。
