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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 01, 2019 |
| Title |
Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARa to transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and bKL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals.
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| Overall design |
Liver ChIP-seq profiles were generated by deep sequencing, were profiled in mouse liver in which jmjd3-floxed mice were infected with either AAV-TBG-Cre or GFP for 12 weeks.
Please note that each processed data file was generated from both replicates and is linked to the corresponding rep1 sample records.
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| Contributor(s) |
Byun S, Seok S, Kim Y, Zhang Y, Yau P, Iwamori N, Xu HE, Ma J, Kemper B, Kemper JK |
| Citation(s) |
32042044 |
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| Submission date |
Sep 30, 2019 |
| Last update date |
Feb 18, 2020 |
| Contact name |
Jongsook Kim Kemper |
| E-mail(s) |
jongsook@illinois.edu
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| Phone |
(217) 333-6317
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| Organization name |
University of Illinois at Champaign-Urbana
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| Department |
Department of Molecular & Integrative Physiology
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| Street address |
524 Burrill Hall 407 S. Goodwin Ave
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| City |
Urbana |
| State/province |
Illinois |
| ZIP/Postal code |
61801 |
| Country |
USA |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA574943 |
| SRA |
SRP223699 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138157_RAW.tar |
4.3 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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