ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.

IF 10.7 1区生物学 Q1 CELL BIOLOGY

Developmental cell Pub Date : 2012-03-13 Epub Date: 2012-02-23 DOI:10.1016/j.devcel.2011.12.001

George L Sen, Lisa D Boxer, Dan E Webster, Rose T Bussat, Kun Qu, Brian J Zarnegar, Danielle Johnston, Zurab Siprashvili, Paul A Khavari

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引用次数: 193

Abstract

Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting that it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process.

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ZNF750是p63靶基因，可诱导KLF4驱动终表皮分化。

表皮分化中断是影响25%以上人群的许多疾病的特征。为了寻找主要的分化介质，我们确定了ZNF750在终表皮分化中的要求。ZNF750控制了许多人类皮肤病的突变基因，包括FLG、LOR、LCE3B、ALOXE3和SPINK5。ZNF750通过一个进化保守的C2H2锌指基序诱导祖细胞分化。表皮主调控因子p63结合ZNF750启动子，是诱导ZNF750启动子的必要条件。ZNF750恢复了p63缺失组织的分化，表明它作用于p63的下游。通过分析ZNF750调控基因寻找功能重要的ZNF750靶点，发现了KLF4，这是一种激活表皮晚期分化的转录因子。ZNF750在转录起始位点的多个位点与KLF4结合并控制其表达。因此，ZNF750直接将组织指定因子p63与终末分化效应因子KLF4联系起来，并代表了该过程紊乱的潜在未来靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental cell 生物-发育生物学

CiteScore

18.90

自引率

1.70%

发文量

203

审稿时长

3-6 weeks

期刊介绍： Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.