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The Bromodomain Protein 4 Contributes to the Regulation of Alternative Splicing

Cell Rep. 2019; 
Uppal S, Gegonne A, Chen Q, Thompson PS, Cheng D, Mu J, Meerzaman D, Misra HS, Singer DS
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摘要

The bromodomain protein 4 (BRD4) is an atypical kinase and histone acetyl transferase (HAT) that binds to acetylated histones and contributes to chromatin remodeling and early transcriptional elongation. During transcription, BRD4 travels with the elongation complex. Since most alternative splicing events take place co-transcriptionally, we asked if BRD4 plays a role in regulating alternative splicing. We report that distinct patterns of alternative splicing are associated with a conditional deletion of BRD4 during thymocyte differentiation in vivo. Similarly, the depletion of BRD4 in T cell acute lymphoblastic leukemia (T-ALL) cells alters patterns of splicing. Most alternatively spliced events affected by B... More

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