Sakai Seishin, Maeda Yurie, Saeki Mai, Konno Daijiro, Kawaji Keita, Matsuzaki Fumio, Suzuki Yutaka, Gotoh Yukiko, Kishi Yusuke
Laboratory of Molecular Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Laboratory of Molecular Neurobiology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
Development. 2025 Jul 1;152(13). doi: 10.1242/dev.204564. Epub 2025 Jun 27.
During neuronal differentiation, gene transcription patterns change in response to both intrinsic and extrinsic cues. Chromatin regulation at regulatory elements plays a key role in this process. However, how chromatin accessibility evolves in vivo in cortical neurons remains unclear. Here, we established a method for labeling differentiating neurons with specific birthdates. Using this method, we traced the 4-day differentiation process of in vivo deep-layer excitatory neurons in the mouse embryonic cortex and examined changes in the genome-wide transcription pattern and chromatin accessibility using RNA sequencing and DNase sequencing, respectively. We found that genomic regions of genes linked to mature neuronal functions, including deep layer-specific and stimulus-responsive genes, became accessible even at the embryonic stage. Additionally, our results indicated the involvement of bivalent marks in neural precursor/stem cells and Dmrt3 and Dmrta2 in the regulation of chromatin accessibility during neuronal differentiation. These findings highlight the importance of chromatin regulation in embryonic neurons, enabling the timely activation of neuronal genes during maturation.
在神经元分化过程中，基因转录模式会根据内在和外在信号发生变化。调控元件处的染色质调控在这一过程中起关键作用。然而，在体内皮质神经元中染色质可及性是如何演变的仍不清楚。在这里，我们建立了一种用特定出生日期标记分化神经元的方法。利用这种方法，我们追踪了小鼠胚胎皮质中体内深层兴奋性神经元的4天分化过程，并分别使用RNA测序和DNase测序检测了全基因组转录模式和染色质可及性的变化。我们发现，与成熟神经元功能相关的基因的基因组区域，包括深层特异性基因和刺激反应基因，即使在胚胎阶段也变得可及。此外，我们的结果表明双价标记在神经前体/干细胞中的作用，以及Dmrt3和Dmrta2在神经元分化过程中对染色质可及性的调控作用。这些发现突出了染色质调控在胚胎神经元中的重要性，使得神经元基因在成熟过程中能够及时激活。
