Alternative Mechanisms for DNA Engagement by BET Bromodomain-Containing Proteins.

ABSTRACT: Epigenetic reader domains regulate chromatin structure and modulate gene expression through the recognition of post-translational modifications on histones. Recently, reader domains have also been found to harbor double-stranded (ds) DNA-binding activity, which is as functionally critical as histone association. Here, we explore the dsDNA recognition of the N-terminal bromodomain of the bromodomain and extra-terminal (BET) protein, BRD4. Using protein-observed ¹⁹F NMR, ¹H-¹⁵N HSQC NMR, electrophoretic mobility shift assays (EMSA), and competitive-inhibition assays, we establish the binding surface of dsDNA and find it to be largely overlapping with the acetylated histone (KAc)-binding site. Rather than engaging in electrostatic contacts, we find dsDNA to in

SUBMITTER: Kalra P 

PROVIDER: S-EPMC9682295 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature