Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Chemoproteomics Enabled Discovery of Selective Probes for NuA4 Factor BRD8 Bromodomain-containing proteins frequently reside in multisubunit chromatin complexes with tissue or cell state-specific compositions. Recent studies have revealed tumor-specific dependencies on the BAF complex bromodomain subunit BRD9 that are a result of recurrent mutations afflicting the structure and composition of associated complex members. To enable the study of ligand engaged complex assemblies, we established a chemoproteomics approach using a functionalized derivative of the BRD9 ligand BI-9564 as an affinity matrix. Unexpectedly, in addition to known interactions with BRD9 and associated BAF complex proteins, we identify a previously unreported interaction with members of the NuA4 complex through the bromodomain-containing subunit BRD8. We apply this finding, alongside homology model guided design, to develop chemical biology approaches for the study of BRD8 inhibition, and to arrive at first-in-class selective and cellularly active probes for BRD8. These tools will empower further pharmacological studies of BRD9 and BRD8 within respective BAF and NuA4 complexes.
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The categories of this paper are: developmental
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The categories of this paper are: cancer
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The categories of this paper are: microbiology
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The categories of this paper are: epidemiology
28
The categories of this paper are: communication
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The categories of this paper are: biophysics
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The categories of this paper are: molecular
6
The categories of this paper are: plant
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The categories of this paper are: synthetic
25
The categories of this paper are: bioengineering
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The categories of this paper are: cell
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The categories of this paper are: neuroscience
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The categories of this paper are: pharmacology
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The categories of this paper are: genetics
29
The categories of this paper are: education
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The categories of this paper are: paleontology