Bromodomain containing protein 1 (BRD1) plays critical roles in chromatin acetylation, gene transcription, erythropoiesis, and brain development. BRD1 is also implicated in several human conditions and is a therapeutic target for cancer. Although, the bromodomain is known to bind acetylated histones, how the function of BRD1 is regulated via non-histone acetylation is unexplored. To identify the non-histone acetylome of BRD1, we develop an R585AzF variant carrying photo responsive 4-azido phenylalanine (AzF) via amber suppressor mutagenesis. We demonstrate biochemical integrity of the AzF-containing analogue and its ability to crosslink non-histone interacting partners present in human cells. Subsequent proteomic experiments led to the identification of the novel BRD1 interactome representing diverse signaling pathways. As a proof-of-concept demonstration, we validated acetylated PDIA1 protein as a binding partner of BRD1. Our work suggests that BRD1 interacts with additional acetyllysine motifs, beyond those characterized in histone proteins.
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| http://dx.doi.org/10.1039/d2cb00043a | DOI Listing |
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