小柯机器人

德国慕尼黑亥姆霍兹中心Boyan Bonev研究组对发育中小鼠皮层转录调控景观进行了多模式分析，并表明 Neurog2 是一种关键的表观基因组重塑因子。相关论文于2022年2月7日发表在《自然—神经科学》杂志上。

为了系统地绘制小鼠新皮层神经分化的调控图谱，他们分析了单细胞中的基因表达和染色质可及性，并将这些数据与纯化细胞群中增强子活性、DNA 甲基化和三维基因组结构的测定值相结合。这使他我们能够识别数以千计的新增强子、及其预测的靶基因以及增强子激活、表观基因组重塑和基因表达之间的时间关系。他们描述了与多种表观遗传模式中广泛且经常协调变化相关特定神经元转录因子。

此外，他们在功能上证明了 Neurog2 在直接介导增强子活性、DNA 去甲基化、增加染色质可及性和促进体内染色质循环方面的新作用。他们的工作提供了大脑皮层谱系规范的基因调控逻辑的全局视图。

据介绍，多个表观遗传层和转录因子 (TF) 如何相互作用以促进大脑发育在很大程度上是未知的。

附：英文原文

Title: Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler

Author: Noack, Florian, Vangelisti, Silvia, Raffl, Gerald, Carido, Madalena, Diwakar, Jeisimhan, Chong, Faye, Bonev, Boyan

Issue&Volume: 2022-02-07

Abstract: How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression and chromatin accessibility in single cells and integrated these data with measurements of enhancer activity, DNA methylation and three-dimensional genome architecture in purified cell populations. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex. By profiling multiple epigenetic layers and enhancer activity in vivo, the authors show a widespread remodeling of the regulatory landscape during mouse cortical development and identify Neurog2 as a key transcription factor driving this process.

DOI: 10.1038/s41593-021-01002-4

Source: https://www.nature.com/articles/s41593-021-01002-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex