OLIG2 is an in vivo bookmarking transcription factor in the developing neural tube in mouse
OLIG2 is an in vivo bookmarking transcription factor in the developing neural tube in mouse
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OLIG2 是小鼠发育神经管中的体内书签转录因子
DOI：
10.1111/jnc.15746
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发表时间：
2023
影响因子：
4.7
通讯作者：
Kitada Masaaki
中科院分区：
文献类型：
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作者：
Hayashi Shinichi;Oe Souichi;Koike Taro;Seki‐Omura Ryohei;Nakano Yosuke;Hirahara Yukie;Tanaka Susumu;Ito Takeshi;Yasukochi Yoshiki;Higasa Koichiro;Kitada Masaaki
细胞具有通过表观遗传调节可遗传的内在特征，例如DNA甲基化和组蛋白修饰。这些可遗传的特征保持着独特的基因表达模式，是细胞记忆的基础。由于有丝分裂染色体的降解或移位，大多数转录因子对细胞记忆没有贡献。然而，越来越多的体外实验表明，某些转录因子可以保留在有丝分裂染色体上，称为书签。这些转录因子可能有助于细胞记忆的第三种新机制。由于转录因子书签的大多数发现都是在体外报道的，目前在体内知之甚少。在小鼠胚胎的神经管中，我们发现OLIG2是一种调节神经祖细胞增殖以及运动神经元和少突胶质细胞细胞命运的碱性螺旋环螺旋（bHLH）转录因子，它在包括M期在内的每个细胞周期中都与染色质结合。OLIG2染色体定位与有丝分裂细胞特征如组蛋白H3、KI 67的磷酸化和核膜破裂一致。OLIG2的染色体定位由N末端三丝氨酸基序调节。光漂白分析揭示了缓慢的OLIG2迁移率，表明OLIG2对DNA的高亲和力。在Olig2N末端缺失突变小鼠中，神经管中的运动神经元和少突胶质细胞祖细胞数量减少，表明书签调节结构域对Olig2功能很重要。我们的结论是，OLIG2是一个从头在体内书签转录因子。我们的研究结果表明，在活的生物体中存在体内书签，并说明了一种新的功能的转录因子。
Cells possess intrinsic features that are inheritable via epigenetic regulation, such as DNA methylation and histone modification. These inheritable features maintain a unique gene expression pattern, underlying cellular memory. Because of the degradation or displacement of mitotic chromosomes, most transcription factors do not contribute to cellular memory. However, accumulating in vitro evidence indicates that some transcription factors can be retained in mitotic chromosomes called as bookmarking. Such transcription factors may contribute to a novel third mechanism of cellular memory. Since most findings of transcription factor bookmarking have been reported in vitro, little is currently known in vivo. In the neural tube of mouse embryos, we discovered that OLIG2, a basic helix loop helix (bHLH) transcription factor that regulates proliferation of neural progenitors and the cell fate of motoneurons and oligodendrocytes, binds to chromatin through every cell cycle including M‐phase. OLIG2 chromosomal localization coincides with mitotic cell features such as the phosphorylation of histone H3, KI67, and nuclear membrane breakdown. Chromosomal localization of OLIG2 is regulated by an N‐terminus triple serine motif. Photobleaching analysis revealed slow OLIG2 mobility, suggesting a high affinity of OLIG2 to DNA. InOlig2N‐terminal deletion mutant mice, motoneurons and oligodendrocyte progenitor numbers are reduced in the neural tube, suggesting that the bookmarking regulatory domain is important for OLIG2 function. We conclude that OLIG2 is a de novo in vivo bookmarking transcription factor. Our results demonstrate the presence of in vivo bookmarking in a living organism and illustrate a novel function of transcription factors.