2023-05-08 マサチューセッツ工科大学(MIT)
◆MITの研究者らは、新しい技術を使って、これらの相互作用を以前より100倍高い分解能でマッピングできることを示しました。これにより、遺伝子とその調節要素の相互作用を低コストで解明できる可能性があり、疾患の発症と治療方法を理解する上で重要な役割を果たすことができると考えられます。
<関連情報>
- https://news.mit.edu/2023/unprecedented-view-3d-genome-0508
- https://www.nature.com/articles/s41588-023-01391-1
リージョン・キャプチャーMicro-Cにより、エンハンサーとプロモーターが入れ子状になったマイクロコンパートメントに合体していることが明らかになった Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments
Viraat Y. Goel,Miles K. Huseyin & Anders S. Hansen
Nature Genetics Published:08 May 2023
DOI:https://doi.org/10.1038/s41588-023-01391-1
Abstract
Although enhancers are central regulators of mammalian gene expression, the mechanisms underlying enhancer–promoter (E-P) interactions remain unclear. Chromosome conformation capture (3C) methods effectively capture large-scale three-dimensional (3D) genome structure but struggle to achieve the depth necessary to resolve fine-scale E-P interactions. Here, we develop Region Capture Micro-C (RCMC) by combining micrococcal nuclease (MNase)-based 3C with a tiling region-capture approach and generate the deepest 3D genome maps reported with only modest sequencing. By applying RCMC in mouse embryonic stem cells and reaching the genome-wide equivalent of ~317 billion unique contacts, RCMC reveals previously unresolvable patterns of highly nested and focal 3D interactions, which we term microcompartments. Microcompartments frequently connect enhancers and promoters, and although loss of loop extrusion and inhibition of transcription disrupts some microcompartments, most are largely unaffected. We therefore propose that many E-P interactions form through a compartmentalization mechanism, which may partially explain why acute cohesin depletion only modestly affects global gene expression.
