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| Status |
Public on Apr 30, 2020 |
| Title |
Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [GRO-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Histone deacetylase 3 (HDAC3) is unique among the HDAC superfamily of chromatin modifiers that silence transcription through enzymatic modification of histones, because interaction with nuclear receptor corepressors (NCoR1/2) is required for engagement of its catalytic activity. However, loss of HDAC3 also represses transcription. Here we report that, during lipopolysaccharide (LPS) activation of macrophages, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound enhancers that repress anti-inflammatory genes. By contrast, LPS-stimulated recruitment of HDAC3 to ATF2-bound sites without NCoR1/2 activates pro-inflammatory genes by a non-canonical mechanism whereby catalytically inactive HDAC3 stably interacts with p65. Consistent with this bimodal inflammatory modulation, deletion of HDAC3 in macrophages safeguards mice from lethal exposure to LPS, but this protection is not conferred by genetic or pharmacological abolition of HDAC3 catalytic activity. Thus, HDAC3 is a dichotomous transcriptional activator and repressor whose deacetylase-independent functions are critical in priming the innate immune system.
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| |
|
| Overall design |
Nascent RNA profiling of bone marrow-derived macrophages untreated macrophages or macrophages treated for 4 hours with either vehicle control (PBS) or LPS (5ng/ml for 4 hours)
|
| |
|
| Contributor(s) |
Nguyen HC, Lazar MA |
| Citation(s) |
32760002 |
| |
| Submission date |
Nov 18, 2019 |
| Last update date |
Aug 07, 2020 |
| Contact name |
Hoang Nguyen |
| E-mail(s) |
hoang.buinguyen@pennmedicine.upenn.edu
|
| Phone |
(215) 898-0198
|
| Organization name |
University of Pennsylvania Perelman School of Medicine
|
| Street address |
3400 Civic Center Boulevard
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104-5160 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE140611 |
Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses |
|
| Relations |
| BioProject |
PRJNA590194 |
| SRA |
SRP230423 |
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