Nepita Irene, Piazza Simonluca, Ruglioni Martina, Cristiani Sofia, Bosurgi Emanuele, Salvadori Tiziano, Vicidomini Giuseppe, Diaspro Alberto, Castello Marco, Cerase Andrea, Bianchini Paolo, Storti Barbara, Bizzarri Ranieri
Nanoscopy, Istituto Italiano di Tecnologia, Via E. Melen 83, 16152 Genova, Italy.
Molecular Microscopy and Spectroscopy, Istituto Italiano di Tecnologia, Via E. Melen 83, 16152 Genova, Italy.
Biology (Basel). 2023 Feb 26;12(3):374. doi: 10.3390/biology12030374.
The genomes of metazoans are organized at multiple spatial scales, ranging from the double helix of DNA to whole chromosomes. The intermediate genomic scale of kilobases to megabases, which corresponds to the 50-300 nm spatial scale, is particularly interesting, as the 3D arrangement of chromatin is implicated in multiple regulatory mechanisms. In this context, polycomb group (PcG) proteins stand as major epigenetic modulators of chromatin function, acting prevalently as repressors of gene transcription by combining chemical modifications of target histones with physical crosslinking of distal genomic regions and phase separation. The recent development of super-resolution microscopy (SRM) has strongly contributed to improving our comprehension of several aspects of nano-/mesoscale (10-200 nm) chromatin domains. Here, we review the current state-of-the-art SRM applied to PcG proteins, showing that the application of SRM to PcG activity and organization is still quite limited and mainly focused on the 3D assembly of PcG-controlled genomic loci. In this context, SRM approaches have mostly been applied to multilabel fluorescence in situ hybridization (FISH). However, SRM data have complemented the maps obtained from chromosome capture experiments and have opened a new window to observe how 3D chromatin topology is modulated by PcGs.
后生动物的基因组在多个空间尺度上进行组织，范围从DNA的双螺旋到整条染色体。几千碱基到几兆碱基的中间基因组尺度，对应于50 - 300纳米的空间尺度，特别引人关注，因为染色质的三维排列涉及多种调控机制。在这种情况下，多梳蛋白家族（PcG）作为染色质功能的主要表观遗传调节剂，主要通过将靶组蛋白的化学修饰与远端基因组区域的物理交联及相分离相结合，作为基因转录的抑制因子发挥作用。超分辨率显微镜（SRM）的最新发展极大地有助于提高我们对纳米/中尺度（10 - 200纳米）染色质结构域多个方面的理解。在这里，我们回顾了应用于PcG蛋白的当前最先进的SRM技术，表明SRM在PcG活性和组织方面的应用仍然相当有限，并且主要集中在PcG控制的基因组位点的三维组装上。在这种情况下，SRM方法大多应用于多标记荧光原位杂交（FISH）。然而，SRM数据补充了从染色体捕获实验获得的图谱，并为观察PcG如何调节三维染色质拓扑结构打开了一扇新窗口。
