|
| Status |
Public on Aug 07, 2019 |
| Title |
SirT7 auto-ADPribosylation regulates glucose starvation response through macroH2A1.1 (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Sirtuins are key players in the response to oxidative, metabolic and genotoxic stress, and are involved in genome stability, metabolic homeostasis and aging. Originally described as NAD+-dependent deacetylases, some sirtuins are also characterized by poorly understood mono-ADP-ribosyltransferase (MADPRT) activity. Here we report that the deacetylase SirT7 is a dual sirtuin as it also features auto-MADPRT activity. Molecular and structural evidence suggests that this novel activity occurs at a second previously undefined active site that is physically separated in another domain. Specific abrogation of this activity alters SirT7 chromatin distribution, suggesting a role for this modification in SirT7 chromatin binding specificity and localization. Our studies uncover an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader macroH2A1.1, a histone variant involved in chromatin organization, metabolism and differentiation. Glucose starvation (GS) boosts this interaction and promotes SirT7 re-localization intergenic regions in a macroH2A1-dependent manner, which is required for specific up- or downregulation of a subset of nearby genes upon GS in primary cells and in vivo in the livers of calorie-restricted (CR) Wt and SirT7-/- mice. The level of expression of these genes decreases with age in SirT7-deficient mice, reinforcing the link between Sirtuins, CR and aging. Our work provides a novel perspective about sirtuin duality and suggests a key role for SirT7/macroH2A1.1 axis in mammalian glucose homeostasis, calorie restriction signaling and aging.
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| |
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| Overall design |
Chromatin from 14.5 day WT and SirT7-/- MEFs was subjected to ChIP using antibodies raised against SIRT7, macroH2A1.1, and H3K27me3, and subjected to high-throughput sequencing.
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| Contributor(s) |
Thackray JK, Serrano L, Simonet NG, Vaquero A |
| Citation(s) |
32832656 |
| Submission date |
Mar 18, 2019 |
| Last update date |
Sep 08, 2020 |
| Contact name |
Joshua K Thackray |
| E-mail(s) |
thackray@rutgers.edu
|
| Organization name |
Rutgers University
|
| Department |
Human Genetics Institute of New Jersey
|
| Lab |
Jay Tischfield Lab
|
| Street address |
145 Bevier Road
|
| City |
Piscataway |
| State/province |
NEW JERSEY |
| ZIP/Postal code |
08854 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (28)
|
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| This SubSeries is part of SuperSeries: |
| GSE128894 |
SirT7 auto-ADPribosylation regulates glucose starvation response through macroH2A1.1 |
|
| Relations |
| BioProject |
PRJNA527842 |
| SRA |
SRP188760 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128487_ChIP-SIRT7-WT-GS.GSE128487_pooled.log2_CONTROL.bw |
390.0 Mb |
(ftp)(http) |
BW |
| GSE128487_ChIP-SIRT7-WT-NT.GSE128487_pooled.log2_CONTROL.bw |
389.3 Mb |
(ftp)(http) |
BW |
| GSE128487_GS_peaks.gIDR_1.3.bed.gz |
30.9 Kb |
(ftp)(http) |
BED |
| GSE128487_KO-GSE128487_NT_4_segments.bed.gz |
1.3 Mb |
(ftp)(http) |
BED |
| GSE128487_KO-GS_4_segments.bed.gz |
1.9 Mb |
(ftp)(http) |
BED |
| GSE128487_NT_peaks.gIDR_1.3.bed.gz |
1.1 Kb |
(ftp)(http) |
BED |
| GSE128487_WT-GSE128487_NT_4_segments.bed.gz |
1.8 Mb |
(ftp)(http) |
BED |
| GSE128487_WT-GS_4_segments.bed.gz |
1.7 Mb |
(ftp)(http) |
BED |
| GSE128487_pooled_GSE128487_ChIP_H3K27me3_KO-GS.rpkm_norm.log2_INPUT.bw |
252.1 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_H3K27me3_KO-NT.rpkm_norm.log2_INPUT.bw |
281.8 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_H3K27me3_WT-GS.rpkm_norm.log2_INPUT.bw |
256.2 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_H3K27me3_WT-NT.rpkm_norm.log2_INPUT.bw |
258.5 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_mH2A1_KO-GS.rpkm_norm.log2_INPUT.bw |
338.3 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_mH2A1_KO-NT.rpkm_norm.log2_INPUT.bw |
335.7 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_mH2A1_WT-GS.rpkm_norm.log2_INPUT.bw |
332.3 Mb |
(ftp)(http) |
BW |
| GSE128487_pooled_GSE128487_ChIP_mH2A1_WT-NT.rpkm_norm.log2_INPUT.bw |
323.0 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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