慕尼黑工业大学Bernhard Kuster小组的一项最新研究报道了人类蛋白质组可以直接接触到DNA。2025年5月22日出版的《细胞》发表了这项成果。

研究小组已经开发了一种“零距离”光交联方法来量化与活细胞中DNA直接接触的蛋白质。从人类乳腺癌细胞中收集DNA相互作用组，该研究组展示了超过一种具有物理访问DNA的蛋白质和数百个肽-核苷酸交联的图谱，以单氨基酸分辨率精确定位蛋白质-DNA界面。来自不同处理细胞的DNA相互作用组的定量比较概括了关键转录因子和DNA修复蛋白的募集，并在几分钟的时间尺度上揭示了染色质可及性的速效限制因子。这开辟了一种直接的方式来探索基因组调控的假设自由的方式，适用于许多生物体和系统。

据了解，在人类细胞中，DNA与组蛋白、RNA和染色质相关蛋白包裹在一起，形成一种有凝聚力的凝胶。在任何给定的时刻，只有蛋白质组的一个子集能够物理地接触到DNA，并组织其结构、转录、复制、修复和其他基本的分子功能。

附：英文原文

Title: The human proteome with direct physical access to DNA

Author: Jakob Trendel, Simon Trendel, Shuyao Sha, Franziska Greulich, Sandra Goll, Susanne I. Wudy, Karin Kleigrewe, Stefan Kubicek, N. Henriette Uhlenhaut, Bernhard Kuster

Issue&Volume: 2025-05-22

Abstract: In a human cell, DNA is packed with histones, RNA, and chromatin-associated proteins, forming a cohesive gel. At any given moment, only a subset of the proteome has physical access to the DNA and organizes its structure, transcription, replication, repair, and other essential molecular functions. We have developed a “zero-distance” photo-crosslinking approach to quantify proteins in direct contact with DNA in living cells. Collecting DNA interactomes from human breast cancer cells, we present an atlas of over one thousand proteins with physical access to DNA and hundreds of peptide-nucleotide crosslinks pinpointing protein-DNA interfaces with single-amino-acid resolution. Quantitative comparisons of DNA interactomes from differentially treated cells recapitulate the recruitment of key transcription factors as well as DNA repair proteins and uncover fast-acting restrictors of chromatin accessibility on a timescale of minutes. This opens a direct way to explore genomic regulation in a hypothesis-free manner, applicable to many organisms and systems.

DOI: 10.1016/j.cell.2025.04.037

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00507-0