小柯机器人

法国蒙彼利埃大学Marcelo Nollmann、Mounia Lagha等研究人员合作发现，顺式调节染色质环出现在TAD和基因激活之前，并且与果蝇早期发育过程中的细胞命运无关。相关论文于2021年4月1日在线发表在《自然—遗传学》杂志上。

研究人员采用Hi-M（单细胞空间基因组学方法）来检测了果蝇早期发育过程中拓扑关联域（TAD）中的顺式调控模块（CRM）-启动子环相互作用。通过比较备用细胞类型中的顺式调节环，研究人员表明物理接近性不一定指示转录状态。

此外，多方分析显示，多个CRM在空间上合并形成枢纽。在TAD出现之前，发育的早期就建立了环和CRM枢纽。此外，CRM枢纽部分地是通过先驱转录因子Zelda的作用而形成的，并先于转录激活。这个方法提供了对CRM-启动子相互作用在定义转录状态以及不同细胞类型中作用的深入了解。 

据悉，细胞命运的获得被认为依赖于远程顺式调控模块，例如增强子和靶标启动子的特定相互作用。然而，染色质结构和基因表达之间的精确相互作用仍然不清楚，特别是在多细胞发育生物中。

附：英文原文

Title: Cis -regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development

Author: Sergio Martin Espinola, Markus Gtz, Maelle Bellec, Olivier Messina, Jean-Bernard Fiche, Christophe Houbron, Matthieu Dejean, Ingolf Reim, Andrs M. Cardozo Gizzi, Mounia Lagha, Marcelo Nollmann

Issue&Volume: 2021-04-01

Abstract: Acquisition of cell fate is thought to rely on the specific interaction of remote cis-regulatory modules (CRMs), for example, enhancers and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly within multicellular developing organisms. In the present study, we employ Hi-M, a single-cell spatial genomics approach, to detect CRM–promoter looping interactions within topologically associating domains (TADs) during early Drosophila development. By comparing cis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses reveal that multiple CRMs spatially coalesce to form hubs. Loops and CRM hubs are established early during development, before the emergence of TADs. Moreover, CRM hubs are formed, in part, via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach provides insight into the role of CRM–promoter interactions in defining transcriptional states, as well as distinct cell types.

DOI: 10.1038/s41588-021-00816-z

Source: https://www.nature.com/articles/s41588-021-00816-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex