|
| Status |
Public on Sep 30, 2011 |
| Title |
Autophagy driven by a master regulator of hematopoiesis |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery function in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis GATA-1 directly activates transcription of genes encoding the essential autophagy component Microtubule Associated Protein 1 Light Chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell type-specific autophagy.
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| |
|
| Overall design |
Genome-wide maps of GATA1 factor occupancy in primary human PBMC derived erythroblasts
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| |
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| Contributor(s) |
Kang Y, Sanalkumar R, O'Geen H, Linnemann AK, Chang C, Bouhassira EE, Farnham PJ, Keles S, Bresnick EH |
| Citation(s) |
22025678, 25115889 |
| |
| Submission date |
Sep 29, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Emery H Bresnick |
| E-mail(s) |
ehbresni@facstaff.wisc.edu
|
| Phone |
608-265-6446
|
| Fax |
608-262-1257
|
| URL |
http://molpharm.wisc.edu/people/faculty/bresnick/bresnick.html
|
| Organization name |
University of Wisconsin School of Medicine and Public Health
|
| Department |
Department of Cell and Regenerative Biology
|
| Lab |
Bresnick Lab
|
| Street address |
1111 Highland Avenue
|
| City |
MADISON |
| State/province |
Wisconsin |
| ZIP/Postal code |
53705 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
|
| Samples (4)
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|
| Relations |
| SRA |
SRP008518 |
| BioProject |
PRJNA147759 |
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