Univ Lyon, Université Claude Bernard Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Evolutive, F-69100, Villeurbanne, France.
Centre de recherche Inria de Lyon, 69603 Villeurbanne, France.
Genome Res. 2022 Feb;32(2):280-296. doi: 10.1101/gr.275901.121. Epub 2021 Dec 20.
Gene expression is regulated through complex molecular interactions, involving -acting elements that can be situated far away from their target genes. Data on long-range contacts between promoters and regulatory elements are rapidly accumulating. However, it remains unclear how these regulatory relationships evolve and how they contribute to the establishment of robust gene expression profiles. Here, we address these questions by comparing genome-wide maps of promoter-centered chromatin contacts in mouse and human. We show that there is significant evolutionary conservation of -regulatory landscapes, indicating that selective pressures act to preserve not only regulatory element sequences but also their chromatin contacts with target genes. The extent of evolutionary conservation is remarkable for long-range promoter-enhancer contacts, illustrating how the structure of regulatory landscapes constrains large-scale genome evolution. We show that the evolution of -regulatory landscapes, measured in terms of distal element sequences, synteny, or contacts with target genes, is significantly associated with gene expression evolution.
基因表达是通过复杂的分子相互作用来调节的，涉及到可以远离其靶基因的顺式作用元件。关于启动子和调节元件之间长距离接触的数据正在迅速积累。然而，这些调节关系如何进化以及它们如何有助于建立稳健的基因表达谱仍然不清楚。在这里，我们通过比较小鼠和人类以启动子为中心的染色质接触的全基因组图谱来解决这些问题。我们表明，-调控景观存在显著的进化保守性，表明选择压力不仅作用于保留调节元件序列，而且作用于它们与靶基因的染色质接触。长距离启动子增强子接触的进化保守性程度非常显著，说明了调控景观的结构如何限制大规模的基因组进化。我们表明，-调控景观的进化，无论是以远端元件序列、同线性还是与靶基因的接触来衡量，都与基因表达的进化显著相关。
