Document Type
Article
Publication Date
5-19-2021
Publication Title
Science Advances
Volume
7
Issue
21
First page number:
1
Last page number:
20
Abstract
Bromodomain and extraterminal proteins (BET) are epigenetic readers that play critical roles in gene regulation. Pharmacologic inhibition of the bromodomain present in all BET family members is a promising therapeutic strategy for various diseases, but its impact on individual family members has not been well understood. Using a transcriptional induction paradigm in neurons, we have systematically demonstrated that three major BET family proteins (BRD2/3/4) participated in transcription with different recruitment kinetics, interdependency, and sensitivity to a bromodomain inhibitor, JQ1. In a mouse model of fragile X syndrome (FXS), BRD2/3 and BRD4 showed oppositely altered expression and chromatin binding, correlating with transcriptional dysregulation. Acute inhibition of CBP/p300 histone acetyltransferase (HAT) activity restored the altered binding patterns of BRD2 and BRD4 and rescued memory impairment in FXS. Our study emphasizes the importance of understanding the BET coordination controlled by a balanced action between HATs with different substrate specificity.
Disciplines
Bioinformatics | Molecular Biology
File Format
File Size
8861 KB
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Kim, S.,
Liu, X.,
Park, J.,
Um, D.,
Kilaru, G.,
Chiang, C.,
Kang, M.,
Huber, K.,
Kang, K.,
Kim, T.
(2021).
Functional Coordination of BET Family Proteins Underlies Altered Transcription Associated With Memory Impairment in Fragile X Syndrome.
Science Advances, 7(21),
1-20.
http://dx.doi.org/10.1126/sciadv.abf7346