Human genetic analysis on the regulation of Duffy gene expression.

Duffy基因的基因组结构已被证明不被内含子分裂，即使在其5 '和3'非翻译区也是如此。与Duffy基因高度同源的IL-8受体基因在编码区不被内含子分裂，而在5 '端非翻译区被分裂。然后，我们重新分析了转录起始位置的5 '-快速扩增cDNA末端（5'-RACE），并确定了一个新的第一外显子和剪接形式的mRNA，这是主要的转录在红细胞和毛细血管后微静脉内皮细胞。新的第一外显子的5 '侧翼区被认为是两种组织的转录控制单位。然而，在内皮细胞的转录起始位置是48个碱基上游的红系细胞。这48个碱基包括一个反向的加塔转录因子的共有结合位点。我们发现纯合的一个碱基取代的加塔基序在黑色的个人与Fy（a-b-）表型。Fy（a-b-）in ...更多信息 已经证明，分化的细胞在骨髓中不产生Duffy mRNA，但在内皮细胞中产生Duffy mRNA。Fy（a-b-）基因表达的组织特异性缺失表明Duffy基因的转录调控受到组织特异性的严格调控。将新的第一外显子的5 '侧翼区插入到CAT报告基因的上游，并分析其转录控制效率。Duffy阳性的启动子序列在红系细胞和内皮细胞中均有效地转录报告基因。当在加塔基序中引入Duffy阴性的一个碱基取代时，在红系细胞中的启动子活性完全减弱。这些数据清楚地解释了黑型Fy（a-b-）中Duffy基因表达的红系特异性破坏。未来必须研究除间日疟原虫以外的选择压力，以拯救Fy（a-b-）个体中沿内皮细胞的Duffy糖蛋白并固定西非的表型。少

The genomic structure of Duffy gene has been shown not to be split by introns, even in its 5' and 3' untranslated regions. The genes of IL-8 receptors, which are the highly homologous genes of Duffy gene, are not split by introns within the coding regions but are split in the 5' untranslated regions. Then we reanalyzed the transcriptional start position by 5'-rapid amplification of cDNA ends (5'-RACE), and identified a novel first exon and spliced form mRNA that was predominant transcript in both erythroid and postcapillary venule endothelium. The 5' flanking region of the novel first exon was regarded as the transcription controlling unit for both tissues. However, the transcriptional start position in endotherium was 48 bases upstream from that of the erythroid cells. And the 48 bases included an inverted consensus binding site for the GATA transcription factor. We found homozygous one base substitution at the GATA motif in black individuals with Fy (a-b-) phenotype. The Fy (a-b-) in … More dividuals have been shown not to produce Duffy mRNA in the bone marrow, but to produce it in endothelial cells. The tissue-specific lacking of expression in Fy (a-b-) indicates that the transcription control of Duffy gene is under tight tissue-specific regulation. The 5' flanking region of the novel first exon was inserted in the upstream of CAT reporter gene and was analyzed the transcription controlling efficiency. The promotor sequence of Duffy positives efficiently transcribed the reporter gene in both erythroid and endothelial cells. When one base substitution of Duffy negatives was introduced in the GATA motif, the promotor activity in erythroid cells was completely diminished. These data clearly explain the erythroid specific disruption of Duffy gene expression in black type Fy (a-b-). The selective pressure other than Plasmodium vivax have to be studied in the future on the saving of Duffy glycoprotein along endothelial cells in Fy (a-b-) individuals and the fixing the phenotype in West Africa. Less