Koga Daisuke, Nakayama Shogo, Higa Tsunaki, Nakayama Keiichi I
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Anticancer Strategies Laboratory, Advanced Research Initiative, Institute of Science Tokyo, Tokyo, Japan.
Genes Cells. 2024 Dec;29(12):1264-1274. doi: 10.1111/gtc.13173. Epub 2024 Oct 11.
The mammalian p57 protein is a member of the CIP/KIP family of cyclin-dependent kinase inhibitors and plays an essential role in the development of multiple tissues during embryogenesis as well as in the maintenance of tissue stem cells in adults. Although several transcription factors have been implicated in regulating the p57 gene, cis-elements such as enhancers that regulate its expression have remained ill-defined. Here we identify a candidate enhancer for the mouse p57 gene (Cdkn1c) within an intron of the Kcnq1 locus by 4C-seq analysis in mouse embryonic stem cells (mESCs). Deletion of this putative enhancer region with the CRISPR-Cas9 system or its suppression by CRISPR interference resulted in a marked attenuation of Cdkn1c expression in differentiating mESCs. Our results thus suggest that this region may serve as an enhancer for the p57 gene during early mouse embryogenesis.
哺乳动物的p57蛋白是细胞周期蛋白依赖性激酶抑制剂CIP/KIP家族的成员，在胚胎发育过程中多种组织的发育以及成体组织干细胞的维持中发挥着重要作用。尽管有几种转录因子参与调控p57基因，但调控其表达的顺式元件如增强子仍不清楚。在这里，我们通过对小鼠胚胎干细胞（mESCs）进行4C-seq分析，在Kcnq1基因座的一个内含子中鉴定出小鼠p57基因（Cdkn1c）的一个候选增强子。用CRISPR-Cas9系统缺失这个假定的增强子区域或通过CRISPR干扰对其进行抑制，导致分化的mESCs中Cdkn1c表达显著减弱。因此，我们的结果表明，该区域可能在小鼠早期胚胎发育过程中作为p57基因的增强子。
