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A genome-wide view of disordered proteins

October 3, 2023
in Science
A genome-wide view of disordered proteins
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Transcription factors containing disordered regions can now be mapped across the genome, aiding functional studies.

Nearly 40% of human proteins are predicted to contain intrinsically disordered regions (IDRs), which can remain unfolded or adopt diverse conformational states in the cell. Although inherently difficult to characterize, IDR-containing proteins are known to have important functions in cellular signaling, the formation of biomolecular condensates and transcriptional regulation. Existing methods to identify intrinsically disordered proteins associating with chromatin have been limited to antibody-based assays. Now, work in Nature Biotechnology by Xing et al.1 introduces DisP-seq, an improved method to map the genome-wide binding of DNA-associated proteins that contain IDRs. This approach uses a small molecule to precipitate proteins containing IDRs along with the genomic regions to which they are bound, followed by massively parallel sequencing of the associated DNA. DisP-seq should provide a valuable tool for investigating IDR-containing DNA-binding proteins, including transcription factors, proteins involved in DNA replication and repair, and oncogenic fusion proteins.

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Fig. 1: DisP-seq identifies genomic regions that contain proteins with intrinsically disordered regions.

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Author information

Authors and Affiliations

Center of Excellence for Data-Driven Discovery, Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA

Benjamin J. Leslie, Benjamin Lang & M. Madan Babu

Corresponding authors

Correspondence to
Benjamin J. Leslie, Benjamin Lang or M. Madan Babu.

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Competing interests

The authors declare no competing interests.

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Cite this article

Leslie, B.J., Lang, B. & Babu, M.M. A genome-wide view of disordered proteins.
Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01955-w

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Published: 02 October 2023

DOI: https://doi.org/10.1038/s41587-023-01955-w

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