Abstract:
Chromatin loops between gene pairs have been observed in diverse contexts in both flies and vertebrates. Combining high-resolution Capture-C, DNA fluorescence in situ hybridization, and genetic perturbations, we dissect the functional role of three loops between genes with related function during Drosophila embryogenesis. By mutating the loop anchor (but not the gene) or the gene (but not loop anchor), we disentangle loop formation and gene expression and show that the 3D proximity of paralogous gene loci supports their co-regulation. Breaking the loop leads to either an attenuation or enhancement of expression and perturbs their relative levels of expression and cross-regulation. Although many loops appear constitutive across embryogenesis, their function can change in different developmental contexts. Taken together, our results indicate that chromatin gene-gene loops act as architectural scaffolds that can be used in different ways in different contexts to fine-tune the coordinated expression of genes with related functions and sustain their cross-regulation.
摘要:
在果蝇和脊椎动物的不同情况下,已经观察到基因对之间的染色质环。结合高分辨率Capture-C,DNA荧光原位杂交,和遗传扰动,我们剖析了果蝇胚胎发生过程中具有相关功能的基因之间的三个环的功能作用。通过突变环锚(但不是基因)或基因(但不是环锚),我们解开了环的形成和基因表达,并表明旁系同源基因位点的3D接近支持它们的共调。破坏环导致表达的减弱或增强,并扰乱它们的相对表达水平和交叉调节。尽管许多环在整个胚胎发生中似乎是组成型的,它们的功能可以在不同的发展环境中变化。一起来看,我们的结果表明,染色质基因-基因环作为结构支架,可以在不同的环境中以不同的方式使用,以微调具有相关功能的基因的协调表达并维持它们的交叉调节.