Luo Zhuojuan, Gao Xin, Lin Chengqi, Smith Edwin R, Marshall Stacy A, Swanson Selene K, Florens Laurence, Washburn Michael P, Shilatifard Ali
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 East Superior Street, Chicago, IL 60611, USA.
Mol Cell. 2015 Feb 19;57(4):685-694. doi: 10.1016/j.molcel.2015.01.007.
The Zinc-finger protein of the cerebellum 2 (Zic2) is one of the vertebrate homologs of the Drosophila pair-rule gene odd-paired (opa). Our molecular and biochemical studies demonstrate that Zic2 preferentially binds to transcriptional enhancers and is required for the regulation of gene expression in embryonic stem cells. Detailed genome-wide and molecular studies reveal that Zic2 can function with Mbd3/NuRD in regulating the chromatin state and transcriptional output of genes linked to differentiation. Zic2 is required for proper differentiation of embryonic stem cells (ESCs), similar to what has been previously reported for Mbd3/NuRD. Our study identifies Zic2 as a key factor in the execution of transcriptional fine-tuning with Mbd3/NuRD in ESCs through interactions with enhancers. Our study also points to the role of the Zic family of proteins as enhancer-specific binding factors functioning in development.
小脑锌指蛋白2（Zic2）是果蝇成对规则基因odd-paired（opa）的脊椎动物同源物之一。我们的分子和生化研究表明，Zic2优先结合转录增强子，并且是胚胎干细胞中基因表达调控所必需的。详细的全基因组和分子研究表明，Zic2可以与Mbd3/NuRD共同作用，调节与分化相关基因的染色质状态和转录输出。与之前关于Mbd3/NuRD的报道类似，Zic2是胚胎干细胞（ESC）正常分化所必需的。我们的研究通过与增强子的相互作用，将Zic2鉴定为ESC中与Mbd3/NuRD一起执行转录微调的关键因子。我们的研究还指出了Zic蛋白家族作为在发育过程中起作用的增强子特异性结合因子的作用。
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