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Series GSE140610 Query DataSets for GSE140610
Status Public on Apr 30, 2020
Title Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
 
Overall design Transcriptomic profiling of bone-marrow derived macrophages (BMDM) harvested from control or MHD3KO mice, or peritoneal macrophages from control, MHD3KO, and NSDAD mice exposed to LPS. BMDM from MHD3KO mice were transduced with retrovirus expressing Y298F or WT HDAC3. BMDM from control and MHD3KO mice were transduced with retrovirus expressing empty vector. BMDM were then treated with vehicle control (PBS), LPS (5ng/ml for 4hour), or IL4 (10ng/ml for 24hour) before RNA were extracted for RNA-seq library preparation. For siRNA experimens, BMDM were transfected with either siControl, siAtf2, siAtf3, or siRela incubated for 48 hours before RNA extraction. Library was prepared with Illumina Truseq kit and sequenced on either Illumina Nextseq 500 or Hiseq 2000/4000 sequencer.
 
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 (4)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (134)
GSM4175208 Control_veh_1 [invitro_LPS]
GSM4175209 Control_veh_2 [invitro_LPS]
GSM4175210 Control_veh_3 [invitro_LPS]
This SubSeries is part of SuperSeries:
GSE140611 Dichotomous Engagement of HDAC3 Activity Governs Inflammatory Responses
Relations
BioProject PRJNA590243
SRA SRP230446

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE140610_SAHA_counts.txt.gz 776.3 Kb (ftp)(http) TXT
GSE140610_invitro_IL4_counts.txt.gz 845.5 Kb (ftp)(http) TXT
GSE140610_invitro_LPS_counts.txt.gz 837.5 Kb (ftp)(http) TXT
GSE140610_invivo_counts.txt.gz 743.9 Kb (ftp)(http) TXT
GSE140610_siRNA_counts.txt.gz 770.8 Kb (ftp)(http) TXT
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Processed data are available on Series record

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