ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
复制标题
DOI：
10.1016/j.devcel.2011.12.001
复制
发表时间：
2012-03-13
影响因子：
11.8
通讯作者：
Khavari, Paul A.
中科院分区：
文献类型：
--
作者：
Sen, George L.;Boxer, Lisa D.;Webster, Dan E.;Bussat, Rose T.;Qu, Kun;Zarnegar, Brian J.;Johnston, Danielle;Siprashvili, Zurab;Khavari, Paul A.
表皮分化中断是影响>25%人群的许多疾病的特征。在寻找分化的主要介质中，我们定义了终末表皮分化对ZNF 750的要求。ZNF 750控制许多人类皮肤病中的突变基因，包括FLG，LOR，LCE 3B，ALOXE 3和SPINK 5。ZNF 750通过进化上保守的C2H2锌指基序诱导祖细胞分化。表皮主调节因子p63与ZNF750启动子结合，是其诱导所必需的。ZNF750恢复了p63缺陷组织的分化，表明其作用于p63下游。通过分析ZNF750调节的基因来寻找功能重要的ZNF750靶点，确定了KLF4，一种激活晚期表皮分化的转录因子。ZNF 750在转录起始位点两侧的多个位点与KLF 4结合并控制其表达。因此，ZNF 750直接将组织特异性因子p63与终末分化效应因子KLF 4联系起来，并代表了该过程障碍的潜在未来靶点。
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 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.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.5
作者：
Yang, Chi-Fan;Hwu, Wuh-Liang;Chen, Yuan-Tsong
通讯作者：
Chen, Yuan-Tsong
影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A
影响因子：
4.3
作者：
Truong, Amy B.;Khavari, Paul A.
通讯作者：
Khavari, Paul A.
影响因子：
30.8
作者：
Segre, JA;Bauer, C;Fuchs, E
通讯作者：
Fuchs, E