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Series GSE134303 Query DataSets for GSE134303
Status Public on Sep 26, 2019
Title The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned non-canonically to coactivate estrogen related receptor a (ERRa), inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues to regulate diurnal metabolic rhythms, and pinpoint a key mechanism by which the microbiota controls host metabolism.
Overall design 1. RNAseq analysis of epithelial cell transcripts in Germ-free WT mice and conventional HDAC3fl/fl and HDAC3ΔIEC mice at 4 time points across a circadian cycle. Laser captured epithelial cells from 3 mice were pooled together for RNAseq at each time point. 2. ChIPseq analysis of epithelial cell H3K9ac and H3K27ac in Germ-free and conventional WT mice and conventional HDAC3fl/fl and HDAC3ΔIEC mice across a circadian cycle. Epithelial cells from 3 mice were pooled together for ChIPseq at each time point. 3. 16s sequencing analysis of fecal bacterial composition in HDAC3fl/fl and HDAC3ΔIEC mice before and after switching from chow diet to high-fat diet.
Contributor(s) Kuang Z, Wang Y, Li Y, Ye C, Ruhn KA, Behrendt CL, Olson EN, Hooper LV
Citation(s) 31604271
Submission date Jul 15, 2019
Last update date Dec 26, 2019
Contact name Zheng Kuang
Organization name UT Southwestern medical center
Department Immunology
Lab Lora Hooper
Street address 6000 Harry Hines Blvd. NA7.500
City Dallas
State/province TX
ZIP/Postal code 75390
Country USA
Platforms (3)
GPL16417 Illumina MiSeq (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (70)
GSM3941640 RNAseq_GF_ZT2
GSM3941641 RNAseq_GF_ZT8
GSM3941642 RNAseq_GF_ZT14
BioProject PRJNA554673
SRA SRP214679

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

Supplementary file Size Download File type/resource
GSE134303_H3K27ac_peaks.txt.gz 434.0 Kb (ftp)(http) TXT
GSE134303_H3K9ac_peaks.txt.gz 556.3 Kb (ftp)(http) TXT
GSE134303_HDAC3_GSE134303_OTU.txt.gz 196.1 Kb (ftp)(http) TXT
GSE134303_OTU_HFD.txt.gz 504.0 Kb (ftp)(http) TXT
GSE134303_RNAseq_FPKM_GF.txt.gz 341.6 Kb (ftp)(http) TXT
GSE134303_RNAseq_FPKM_WT_KO.txt.gz 575.6 Kb (ftp)(http) TXT
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Processed data are available on Series record

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