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| Status |
Public on Nov 17, 2014 |
| Title |
Epigenetic and transcriptional regulation of starvation-induced atrophy and autophagy programs by Foxk1 and Sin3A |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Autophagy is the primary catabolic process triggered in response to starvation. Although autophagic regulation within the cytosolic compartment is well established, it is becoming clear that nuclear events also regulate the induction or repression of autophagy. Nevertheless, a thorough understanding of the mechanisms by which sequence-specific transcription factors modulate expression of genes required for autophagy is lacking. Here, we identify Foxk proteins (Foxk1 and Foxk2) as transcriptional repressors of autophagy in muscle cells and fibroblasts. Interestingly, Foxk1/2 serve to counter-balance another forkhead transcription factor, Foxo3, which induces an overlapping set of autophagic and atrophic targets in muscle. Foxk1/2 specifically recruits Sin3A-HDAC complexes to restrict acetylation of histone H4 and expression of critical autophagy genes. Remarkably, mTOR promotes the transcriptional activity of Foxk1 by facilitating nuclear entry to specifically limit basal levels of autophagy in nutrient-rich conditions. Our study highlights an ancient, conserved mechanism whereby nutritional status is interpreted by mTOR to restrict autophagy by repressing essential autophagy genes via Foxk-Sin3-mediated transcriptional control.
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| Overall design |
Examination of (1) chromatin binding of Foxk1 and Sin3A in non-starved myoblasts and (2) gene expression profiling upon either starvation or siRNA-mediated depletion of Foxk1 relative to a non-starved control.
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| Contributor(s) |
Bowman CJ, Dynlacht BD |
| Citation(s) |
25402684 |
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| Submission date |
Apr 21, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Brian Dynlacht |
| E-mail(s) |
Brian.Dynlacht@nyumc.org
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| Organization name |
New York University School of Medicine
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| Street address |
522 First Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10010 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA244979 |
| SRA |
SRP041311 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56932_RAW.tar |
513.3 Mb |
(http)(custom) |
TAR (of BED, BIGWIG, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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