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Trendel, J.* ; Trendel, S.* ; Sha, S.* ; Greulich, F.* ; Goll, S.* ; Wudy, S.I.* ; Kleigrewe, K.* ; Kubicek, S.* ; Uhlenhaut, N.H. ; Kuster, B.*

The human proteome with direct physical access to DNA.

Cell, DOI: 10.1016/j.cell.2025.04.037 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna-binding Domains ; Dna-binding Proteins ; Dna-interacting Proteome ; Idrs ; Chromatin Proteomics ; Intrinsically Disordered Regions ; Mass Spectrometry ; Nucleotide-peptide Hybrids ; Photo-crosslinking ; Physical Protein-dna Interactions ; Transcription Factors
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Endocrinology (IDE)