Title | BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Korb E, Herre M, Zucker-Scharff I, Darnell RB, C Allis D |
Journal | Nat Neurosci |
Volume | 18 |
Issue | 10 |
Pagination | 1464-73 |
Date Published | 2015 Oct |
ISSN | 1546-1726 |
Keywords | Animals, Azepines, Blotting, Western, Cells, Cultured, Chromatin Immunoprecipitation, Female, Immunohistochemistry, Male, Memory, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Neurons, Nuclear Proteins, Polymerase Chain Reaction, RNA, Small Interfering, Seizures, Transcription Factors, Transcriptional Activation, Transfection, Triazoles |
Abstract | Precise regulation of transcription is crucial for the cellular mechanisms underlying memory formation. However, the link between neuronal stimulation and the proteins that directly interact with histone modifications to activate transcription in neurons remains unclear. Brd4 is a member of the bromodomain and extra-terminal domain (BET) protein family, which binds acetylated histones and is a critical regulator of transcription in many cell types, including transcription in response to external cues. Small molecule BET inhibitors are in clinical trials, yet almost nothing is known about Brd4 function in the brain. Here we show that Brd4 mediates the transcriptional regulation underlying learning and memory. The loss of Brd4 function affects critical synaptic proteins, which results in memory deficits in mice but also decreases seizure susceptibility. Thus Brd4 provides a critical link between neuronal activation and the transcriptional responses that occur during memory formation. |
DOI | 10.1038/nn.4095 |
Alternate Journal | Nat. Neurosci. |
PubMed ID | 26301327 |
PubMed Central ID | PMC4752120 |
Grant List | R01 NS081706 / NS / NINDS NIH HHS / United States R01 GM040922 / GM / NIGMS NIH HHS / United States F32MH103921 / MH / NIMH NIH HHS / United States F32 MH103921 / MH / NIMH NIH HHS / United States R01 NS34389 / NS / NINDS NIH HHS / United States NS081706 / NS / NINDS NIH HHS / United States R01 NS034389 / NS / NINDS NIH HHS / United States / / Howard Hughes Medical Institute / United States P50 MH096890 / MH / NIMH NIH HHS / United States |
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