Regulation of desmocollin gene expression in the epidermis: CCAAT/enhancer-binding proteins modulate early and late events in keratinocyte differentiation
Regulation of desmocollin gene expression in the epidermis: CCAAT/enhancer-binding proteins modulate early and late events in keratinocyte differentiation
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DOI：
10.1042/bj20040077
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发表时间：
2004-06-15
影响因子：
4.1
通讯作者：
Chidgey, M
中科院分区：
文献类型：
--
作者：
Smith, C;Zhu, KC;Chidgey, M
桥粒胶原蛋白（Dscs）是桥粒钙粘蛋白，在表皮中表现出分化特异性表达模式。Dsc 3表达在基底细胞层中最强，而Dsc 1主要局限于上层终末分化层。为了更好地理解Dsc表达在表皮中调节的过程，我们分离了Dsc 3和Dsc 1的5 '侧翼DNA，并分析了它们在原代角质形成细胞中的活性。在本研究中，我们发现CCAAT/增强子结合蛋白家族的转录因子在DSC的表达调节中起作用，并且在这样做时，涉及这类转录因子在角质形成细胞分化的早期和晚期事件中。我们发现Dscs受C/EBP（CCAAT/增强子结合蛋白）家族成员的差异调节，Dsc 3的表达被C/EBP激活，而不是C/EBPalpha，Dsc 1的情况相反。这两种Dscs的表达都是由另一个家族成员C/EBP δ激活的。这些结果首次显示了桥粒钙粘蛋白基因的表达是如何调节的，并为表皮中其他分化特异性基因的控制提供了机制。
Desmocollins (Dscs) are desmosomal cadherins that exhibit differentiation-specific patterns of expression in the epidermis. Dsc3 expression is strongest in basal cell layers, whereas Dsc1 is largely confined to upper, terminally differentiating strata. To understand better the processes by which Dsc expression is regulated in the epidermis, we have isolated Dsc3 and Dsc1 5'-flanking DNAs and analysed their activity in primary keratinocytes. In the present study, we found that transcription factors of the CCAAT/enhancer-binding protein family play a role in the regulation of expression of both Dscs and, in so doing, implicate this class of transcription factors in both early and late events in keratinocyte differentiation. We show that Dscs are differentially regulated by C/EBP (CCAAT/enhancer-binding protein) family members, with Dsc3 expression being activated by C/EBP but not C/EBPalpha, and the reverse being the case for Dsc1. Expression of both Dscs is activated by another family member, C/EBPdelta. These results show for the first time how desmosomal cadherin gene expression is regulated and provide a mechanism for the control of other differentiation-specific genes in the epidermis.