瑞士洛桑大学Maria Cristina Gambetta等研究人员合作发现，果蝇神经系统调控基因组的染色体级组织结构。该项研究成果于2023年8月2日在线发表在《细胞》杂志上。

研究人员发现了以前未报道过的基因组折叠水平的证据，在这种情况下，相隔数百万个碱基对的遥远拓扑关联域（TAD）相互作用，形成元域。在元域中，基因启动子和远距离TAD中的结构性基因间元件特异性配对。相关基因编码神经元决定因子，包括参与轴突导向和粘附的基因。这些长程关联出现在很大一部分神经元中，但只支持一部分神经元的转录。元域由不同的转录因子形成，这些因子能够通过灵活的长距离配对。

研究人员提出的证据表明，GAF和CTCF这两种因子在这一过程中发挥了直接作用。与之前在哺乳动物中描述的那些相比，果蝇的高阶元域相互作用相对简单，这使研究人员能够证明基因组可以折叠成高度特化的细胞类型特异性支架，从而实现兆级规模的调控关联。

据介绍，以前的研究发现TAD是基因组组织的基本单位。

附：英文原文

Title: Chromosome-level organization of the regulatory genome in the Drosophila nervous system

Author: Giriram Mohana, Julien Dorier, Xiao Li, Marion Mouginot, Rebecca C. Smith, Héléna Malek, Marion Leleu, Daniel Rodriguez, Jenisha Khadka, Patrycja Rosa, Pascal Cousin, Christian Iseli, Simon Restrepo, Nicolas Guex, Brian D. McCabe, Aleksander Jankowski, Michael S. Levine, Maria Cristina Gambetta

Issue&Volume: 2023-08-02

Abstract: Previous studies have identified topologically associating domains (TADs) as basicunits of genome organization. We present evidence of a previously unreported levelof genome folding, where distant TAD pairs, megabases apart, interact to form meta-domains.Within meta-domains, gene promoters and structural intergenic elements present indistant TADs are specifically paired. The associated genes encode neuronal determinants,including those engaged in axonal guidance and adhesion. These long-range associationsoccur in a large fraction of neurons but support transcription in only a subset ofneurons. Meta-domains are formed by diverse transcription factors that are able topair over long and flexible distances. We present evidence that two such factors,GAF and CTCF, play direct roles in this process. The relative simplicity of higher-ordermeta-domain interactions in Drosophila, compared with those previously described in mammals, allowed the demonstration thatgenomes can fold into highly specialized cell-type-specific scaffolds that enablemegabase-scale regulatory associations.

DOI: 10.1016/j.cell.2023.07.008

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00741-9