小柯机器人

德国柏林医学系统生物学研究所Darío G. Lupiáñez团队发现，一个成簇-CTCF结构域边界的体内剖析揭示调节绝缘的发育原理。2022年7月11日，《自然—遗传学》杂志在线发表了这项成果。

据研究人员介绍，脊椎动物的基因组组织成拓扑学上的关联域，由将调控元件与非目标基因隔离的边界划定。然而，边界功能是如何建立的并不十分清楚。

Title: In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation

Author: Anania, Chiara, Acemel, Rafael D., Jedamzick, Johanna, Bolondi, Adriano, Cova, Giulia, Brieske, Norbert, Khn, Ralf, Wittler, Lars, Real, Francisca M., Lupiez, Daro G.

Issue&Volume: 2022-07-11

Abstract: Vertebrate genomes organize into topologically associating domains, delimited by boundaries that insulate regulatory elements from nontarget genes. However, how boundary function is established is not well understood. Here, we combine genome-wide analyses and transgenic mouse assays to dissect the regulatory logic of clustered-CCCTC-binding factor (CTCF) boundaries in vivo, interrogating their function at multiple levels: chromatin interactions, transcription and phenotypes. Individual CTCF binding site (CBS) deletions revealed that the characteristics of specific sites can outweigh other factors such as CBS number and orientation. Combined deletions demonstrated that CBSs cooperate redundantly and provide boundary robustness. We show that divergent CBS signatures are not strictly required for effective insulation and that chromatin loops formed by nonconvergently oriented sites could be mediated by a loop interference mechanism. Further, we observe that insulation strength constitutes a quantitative modulator of gene expression and phenotypes. Our results highlight the modular nature of boundaries and their control over developmental processes.

DOI: 10.1038/s41588-022-01117-9

Source: https://www.nature.com/articles/s41588-022-01117-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex