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Chromatin biology

Quantitative proteomics of protein–nucleosome interactions

Nature Genetics volume 56, page 557 (2024)Cite this article

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One mechanism of gene regulation is the recognition of histone post-translational modifications (PTMs) by chromatin-binding proteins, which then recruit the core transcriptional machinery. Although the concept of a ‘histone code’ that corresponds to varying chromatin functional states is established, it remains unclear how combinations of these PTMs are recognized by chromatin binders, which often have multiple modification-binding domains. Lukauskas et al. applied unbiased SILAC-based quantitative affinity-purification proteomics to recombinant dinucleosomes that bear multiple PTMs, representing active and repressive chromatin, and characterized the binding preferences of 1,915 proteins. Binding is often affected by combinatorial PTMs and is consistent within multi-subunit complexes. Interestingly, no protein strongly associated with H3K4me1, supporting the hypothesis that this PTM is not causal for recruiting factors to enhancers. Perturbation of the DNA linkers of the dinucleosomes showed that these act largely independently of histone PTMs for protein recruitment, underlining the importance of nucleosomal positioning. Although the in vitro system does not fully capture the biochemical complexity of cis-regulatory elements and their bound proteome, these results underline that the binding of chromatin by proteins can be mediated by multiple features, and that these combinatorial, synergistic interactions probably have an important role in gene regulation.

Original reference: Nature 627, 671–679 (2024)

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  1. Nature Genetics https://www.nature.com/ng/

    Michael Fletcher

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  1. Michael Fletcher
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Correspondence to Michael Fletcher.

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Fletcher, M. Quantitative proteomics of protein–nucleosome interactions. Nat Genet 56, 557 (2024). https://doi.org/10.1038/s41588-024-01727-5

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