Wu Meng, Zhang Ye, Wu Ning-hua, Shen Yu-fei
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Cell Biochem. 2009 May 15;107(2):264-71. doi: 10.1002/jcb.22122.
Neurogenin1 is an important bHLH protein that plays crucial role in neurogenesis. We first show that the expression of ngn1 increases drastically in RA induced neuronal differentiation. During which, a three successive stages of the epigenetic changes surrounding the ngn1 gene are found correlated with a repression to activation of the gene in P19 cells. Recruiting of a repressive histone code H3K27me3 on the ngn1 gene is the dominant change in first repression stage, which is followed by the binding of the active codes of H3K9ac, H3K14ac, and the H3K4me3 in the second and third stages of RA treatment. Additionally, BRM but not BRG1 is specifically recruited to ngn1 gene at the third stage and is positively involved in the RA induced ngn1 expression. We propose that histone modifiers and chromatin remodelers are pivotal in the activation of the ngn1 gene in RA induced differentiation of P19 cells.
神经生成素1是一种重要的bHLH蛋白,在神经发生过程中发挥关键作用。我们首次表明,在视黄酸(RA)诱导的神经元分化过程中,ngn1的表达急剧增加。在此期间,发现围绕ngn1基因的表观遗传变化的三个连续阶段与P19细胞中该基因从抑制到激活相关。在第一个抑制阶段,ngn1基因上募集抑制性组蛋白编码H3K27me3是主要变化,随后在RA处理的第二和第三阶段,活性编码H3K9ac、H3K14ac和H3K4me3与之结合。此外,在第三阶段,BRM而非BRG1特异性地募集到ngn1基因上,并积极参与RA诱导的ngn1表达。我们提出,组蛋白修饰剂和染色质重塑剂在RA诱导P19细胞分化过程中ngn1基因的激活中起关键作用。