Evidence for local control of gene expression in the epidermal differentiation complex
Evidence for local control of gene expression in the epidermal differentiation complex
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DOI：
10.1034/j.1600-0625.2002.110503.x
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Zhao, XP
中科院分区：
文献类型：
--
作者：
Elder, JT;Zhao, XP
表皮分化复合物 (EDC) 位于染色体带 1q21 上，由至少 43 个在角质形成细胞分化过程中表达的基因组成。我们发现人类角质形成细胞和成纤维细胞中两个 EDC 基因（S100A2 和 S00A6）的表达与 DNA 甲基化之间存在负相关，这表明染色质结构在 EDC 基因表达的组织特异性中的作用。 5-氮杂胞苷 (5AC) 和丁酸钠 (NaB) 是已知可促进“开放”染色质结构的两种试剂。为了探索染色质结构和角质形成细胞分化之间的关系，我们用 5AC 或 NaB 或已知促进其终末分化的方案处理正常人角质形成细胞 (NHK)。然后，我们通过 Northern blotting 测量了几个 S100 基因、小脯氨酸富集区 1、-2 和 -3、兜甲蛋白和外皮蛋白的稳态 mRNA 水平。 5AC和NaB均显着增加NHK中SPRR1/2和外皮蛋白的表达。相反，两种药物以及角质形成细胞分化的诱导均降低了S100A2的表达。此外，虽然聚集的 EDC 基因表现出在上皮细胞中表达的总体趋势，但它们表现出不同的细胞类型特异性表达模式。这些结果表明，局部基因特异性因素在角质形成细胞谱系中和角质形成细胞终末分化过程中 EDC 基因表达的调节中发挥重要作用。
The epidermal differentiation complex (EDC), located on chromosomal band 1q21, consists of at least 43 genes that are expressed during keratinocyte differentiation. Indicative of a role for chromatin structure in tissue specificity of EDC gene expression, we identified an inverse correlation between expression and DNA methylation for two EDC genes (S100A2 and S00A6) in human keratinocytes and fibroblasts. 5-azacytidine (5AC) and sodium butyrate (NaB) are two agents known to promote 'open' chromatin structure. To explore the relationship between chromatin structure and keratinocyte differentiation, we treated normal human keratinocytes (NHK) with 5AC or NaB, or with protocols known to promote their terminal differentiation. We then measured the steady-state mRNA levels for several S100 genes, small proline rich region-1, -2, and -3, loricrin, and involucrin by Northern blotting. 5AC and NaB each markedly increased expression of SPRR1/2 and involucrin in NHK. In contrast, expression of S100A2 was reduced by both agents, and by induction of keratinocyte differentiation. Moreover, while the clustered EDC genes displayed a general tendency to be expressed in epithelial cells, they displayed different patterns of cell type-specific expression. These results indicate that local, gene-specific factors play an important role in the regulation of EDC gene expression in the keratinocyte lineage and during keratinocyte terminal differentiation.