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首页> 外文期刊>Molecular and Cellular Biology >Positive and negative elements regulate a melanocyte-specific promoter.
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Positive and negative elements regulate a melanocyte-specific promoter.

机译：正负元素调节黑素细胞特异性启动子。

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Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.
机译：黑色素细胞是驻留在人表皮的毛囊，眼睛和基底层中的专门细胞，其主要功能是色素黑色素的产生，引起皮肤，头发和眼睛的颜色。黑色素生成是黑色素细胞特有的一个过程，涉及通过许多黑色素细胞特异性酶（包括酪氨酸酶和酪氨酸酶相关蛋白1（TRP-1））对酪氨酸的加工，仅在与黑色素细胞前体黑素细胞分化后发生。在人类中，可通过紫外线照射诱导黑色素生成，黑色素从表皮中的黑色素细胞转移到周围的角质形成细胞中，以保护免受紫外线引起的伤害。然而，过度暴露于紫外线是恶性黑色素瘤的一种主要原因，恶性黑色素瘤是一种日益普遍且高度侵袭性的疾病。作为了解黑素细胞分化和黑素细胞特异性转录调控的初步方法，我们分离了编码TRP-1的基因，并研究了细胞类型特异性表达所需的顺式和反式作用因子。我们发现，TRP-1启动子同时包含正向和负向调控元件，可在表达TRP-1的有色黑色素瘤细胞系中有效表达，而在NIH 3T3或JEG3细胞中则不会，并且最小的启动子在-44和+之间延伸107对于细胞类型特异性表达就足够了。 DNA-蛋白质相互作用与广泛诱变相结合的分析确定了三个因素，其结合与两个正调控元素和一个负调控元素的功能相关。这些因子之一，称为M-box-binding factor 1，结合11 bp的基序M盒，尽管完全保守，但M盒在表达TRP-1和不表达TRP-1的细胞系中均充当阳性调节元件。在黑素细胞特异性酪氨酸酶和TRP-1启动子之间。讨论了黑素细胞特异性基因表达的潜在机制。

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