Prominent chromatin loops have been observed in both flies and vertebrates, and these often involve genes either with related functions or that are paralogs, pointing to a functional relevance for their co-regulation. Pollex et al. dissected the contribution of three loops formed between genes with related functions to the regulation of their own expression during Drosophila embryogenesis. They achieved this by quantifying the effect of perturbing both loop formation and gene expression. They showed that breaking the loop by mutating its anchor without affecting the gene resulted in either an increase or decrease in the expression of the gene at the other end of the loop. This was even true for large genomic distances, for instance the 2.6-Mb loop between the GluRIA and GluRIB genes that is formed in differentiating neurons. Interestingly, the majority of loops appear to be constitutive throughout embryogenesis, but their effect on modulating the relative expression levels of two genes can vary depending on the tissue context or developmental stage. Together, these findings highlight a topological role for paralog gene–gene loops in facilitating the cross-regulation of their co-expression in a flexible manner, either boosting or attenuating co-expression.

Original reference: Mol. Cell 84, 822–838.e8 (2024)

在果蝇和脊椎动物中都观察到了显着的染色质环，这些环通常涉及具有相关功能或旁系同源的基因，表明它们的共同调节具有功能相关性。波莱克斯等人。剖析了果蝇胚胎发生过程中具有相关功能的基因之间形成的三个环对自身表达调节的贡献。他们通过量化扰乱环形成和基因表达的影响来实现这一目标。他们表明，通过突变锚点来打破环而不影响基因，会导致环另一端基因表达的增加或减少。对于较大的基因组距离也是如此，例如在分化神经元中形成的GluRIA和GluRIB基因之间的 2.6 Mb 环。有趣的是，大多数环似乎在整个胚胎发生过程中都是组成性的，但它们对调节两个基因相对表达水平的影响可能会根据组织背景或发育阶段而变化。总之，这些发现强调了旁系同源基因-基因环在以灵活的方式促进其共表达的交叉调节（增强或减弱共表达）方面的拓扑作用。

原始参考文献： Mol.细胞 84 , 822–838.e8 (2024)