Chen Zhong, Song Lijuan, Chen Wanqiu, Wang Charles
Center for Genomics, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Commun Biol. 2025 Sep 1;8(1):1326. doi: 10.1038/s42003-025-08683-8.
Histone H3K4me1 and H3K27me3 modifications play a crucial role in regulating neuronal development by maintaining the balance between active and inactive genes during neurogenesis. Prenatal exposure to electronic-cigarette (e-cig) aerosol has been shown to alter neuronal differentiation in a neuron type-specific manner. However, it remains unclear whether e-cig aerosol exposure affects gene expression by altering H3K4me1 and H3K27me3 modifications. Using single-nucleus joint profiling of H3K4me1-H3K27me3 and transcriptome of neonatal rat prefrontal cortex, we demonstrate that e-cig aerosol exposure alters the H3K4me1-H3K27me3 methylation patterns in the promoters, i.e., the bivalency, of many cell type-specific genes, impacting gene expression levels, neuronal differentiation and functions. Additionally, the prenatal e-cig aerosol exposure impacts the expression of genes related to circadian entrainment, calcium signaling, protein kinase signaling transduction, and synaptic transmission. These results suggest that nicotine addiction may be epigenetically imprinted at a very early stage of brain development.
组蛋白H3K4me1和H3K27me3修饰在神经发生过程中通过维持活跃基因和非活跃基因之间的平衡，对调节神经元发育起着至关重要的作用。已有研究表明，产前暴露于电子烟气溶胶会以神经元类型特异性的方式改变神经元分化。然而，目前尚不清楚电子烟气溶胶暴露是否通过改变H3K4me1和H3K27me3修饰来影响基因表达。通过对新生大鼠前额叶皮质进行H3K4me1-H3K27me3单核联合分析和转录组分析，我们证明电子烟气溶胶暴露会改变许多细胞类型特异性基因启动子中的H3K4me1-H3K27me3甲基化模式，即双价性，从而影响基因表达水平、神经元分化和功能。此外，产前电子烟气溶胶暴露会影响与昼夜节律调节、钙信号传导、蛋白激酶信号转导和突触传递相关的基因表达。这些结果表明，尼古丁成瘾可能在大脑发育的非常早期阶段就通过表观遗传方式被印记下来。
