The role of calcium-responsive element located in human keratin 1 gene on keratinocyte differentiation

哺乳动物的表皮是不断更新的层状鳞状上皮。表皮的主要细胞类型是表皮角质形成细胞。角质形成细胞经过严格调控、高度区隔化的分化过程，形成成熟的层状表皮。表皮的基底层含有增殖的角质形成细胞。作为对分化信号的反应，这些细胞停止分裂，同时成熟并通过表皮的棘和颗粒层迁移。最终，它们被转化成扁平的鳞片，并脱落到环境中。角蛋白1 （K1）基因的表达受到严格调控，并与角化细胞的明显分化状态相一致。K1的转录主要定位于棘层。对大约6 kb的5'序列进行评估表明，这些序列具有组织特异性和分化特异性表达所需的信息。对远端序列的调查确定了sp1位点。这两个位点中的任何一个发生突变，都会破坏结合，导致启动子活性显著降低。含有远端元件的序列，虽然是高水平表达所必需的，但在Sp1的存在下，会导致显著的抑制。总的来说，这些数据确定并描述了几个调控元件，这些元件相互合作，导致hK1基因的适当的组织特异性、发育特异性和分化特异性表达。

The mammalian epidermis is a constantly renewing stratified squamous epithelium. The major cell type of the epidermis is the epidermal keratinocyte. Keratinocytes undergo a strictly regulated, highly compartmentalized differentiation process that results in a mature stratified epidermis. The basal layer of the epidermis contains proliferating keratinocytes. In response to differentiating signals, these cells stop dividing and simultaneously mature and migrate through the spinous and granular layers of the epidermis. Ultimately, they are transformed into flattened squamas and sloughed into the environment. Expression of the Keratin 1 (K1) gene is tightly regulated and is coincident with a distinct differentiation state of keratinocytes. Transcription of K1 is primarily localized to the spinous layer. Evaluation of approximately 6 kb of 5' franking sequence indicated that these sequences possessed the information required for tissue-and differentiation-specific expression. Investigation of distal sequences identified Sp 1 site. Mutation of either of these sites, which ablated binding, resulted in significant decreases in promoter activity. Sequences containing the distal element, while required for high levels of expression, were responsible for significant suppression in the presence of Sp1. Collectively, these data identify and characterize several regulatory elements that cooperate to cause the appropriate tissue-, developmental-, and differentiation-specific expression of the hK1 gene.