最早在人类β珠蛋白基因座中发现的位点控制区(locus control regions,LCR)对于珠蛋白基因在红细胞分化和发育过程中的特异性表达起着重要作用。LCR位于珠蛋白基因上游6—25kb,由至少7个DNaseI超敏感位点所组成,具有很强的增强子活性,可以激活和促进珠蛋白基因的转录。LCR增强子活性具有组织特异性,并与拷贝数成正比。此外,LCR还参与基因在细胞核内的定位、组蛋白修饰、染色质开放、边界结构域形成,以及DNA复制起始等精细调控过程。有多个模型阐述LCR远程调控基因表达的分子机制,被普遍接受的是成环模型(looping model)。在生长激素(GH)、TH2细胞因子、MHCII等基因区域也发现有类似珠蛋白的LCR结构,都在深入研究之中。
The locus control region (LCR) was first identified in the human β globin locus. It plays an important role of regulating gene expression in differentiation and development of erythrocyte. The LCR is located 6 - 25 kb upstream of the first globin gene and consists of 7 DNase I hypersensitive sites. The most prominent property of the LCR is their strong transcription-enhancing activity. LCR can also participate in histone modification, chromatin ‘open', nuclear localization, domain boundaries formation, and timing and origin of DNA replication. Four models of LCR function have been proposed, while most of the experimental results support the looping model. Besides in β globin locus, LCRs are found in the loci of growth hormone, TH2 cytokine, MHCII and many other genes.