Decoding the genomic landscape of chromatin-associated biomolecular condensates

Zhaowei Yu, Qi Wang, Qichen Zhang, Yawen Tian, Guo Yan, Jidong Zhu, Guangya Zhu () and Yong Zhang ()
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Zhaowei Yu: Tongji University
Qi Wang: Tongji University
Qichen Zhang: Naval Medical University
Yawen Tian: Lingang Laboratory
Guo Yan: Lingang Laboratory
Jidong Zhu: Etern Biopharma
Guangya Zhu: Lingang Laboratory
Yong Zhang: Tongji University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Biomolecular condensates play a significant role in chromatin activities, primarily by concentrating and compartmentalizing proteins and/or nucleic acids. However, their genomic landscapes and compositions remain largely unexplored due to a lack of dedicated computational tools for systematic identification in vivo. To address this, we develop CondSigDetector, a computational framework designed to detect condensate-like chromatin-associated protein co-occupancy signatures (CondSigs), to predict genomic loci and component proteins of distinct chromatin-associated biomolecular condensates. Applying this framework to mouse embryonic stem cells (mESC) and human K562 cells enable us to depict the high-resolution genomic landscape of chromatin-associated biomolecular condensates, and uncover both known and potentially unknown biomolecular condensates. Multi-omics analysis and experimental validation further verify the condensation properties of CondSigs. Additionally, our investigation sheds light on the impact of chromatin-associated biomolecular condensates on chromatin activities. Collectively, CondSigDetector provides an approach to decode the genomic landscape of chromatin-associated condensates, facilitating a deeper understanding of their biological functions and underlying mechanisms in cells.

Date: 2024
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DOI: 10.1038/s41467-024-51426-2

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