PUBLICATION
SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis
- Authors
- Andrade, D., Velinder, M., Singer, J., Maese, L., Bareyan, D., Nguyen, H., Chandrasekharan, M.B., Lucente, H., McClellan, D., Jones, D., Sharma, S., Liu, F., Engel, M.E.
- ID
- ZDB-PUB-160310-16
- Date
- 2016
- Source
- Molecular and cellular biology 36(10): 1438-50 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Binding Sites
- COS Cells
- Cell Differentiation
- Chlorocebus aethiops
- Gene Expression Regulation
- HEK293 Cells
- HL-60 Cells
- Hematopoiesis*
- Histone Demethylases/metabolism*
- Humans
- Lysine/metabolism
- Mice
- Molecular Chaperones/chemistry
- Molecular Chaperones/metabolism*
- NIH 3T3 Cells
- Protein Binding
- Protein Inhibitors of Activated STAT/chemistry
- Protein Inhibitors of Activated STAT/metabolism*
- Proto-Oncogene Proteins/chemistry
- Proto-Oncogene Proteins/metabolism*
- Proto-Oncogene Proteins c-myc/metabolism*
- Repressor Proteins/chemistry
- Repressor Proteins/metabolism*
- Sumoylation
- PubMed
- 26951200 Full text @ Mol. Cell. Biol.
Citation
Andrade, D., Velinder, M., Singer, J., Maese, L., Bareyan, D., Nguyen, H., Chandrasekharan, M.B., Lucente, H., McClellan, D., Jones, D., Sharma, S., Liu, F., Engel, M.E. (2016) SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis. Molecular and cellular biology. 36(10):1438-50.
Abstract
Cell fate specification requires precise coordination of transcription factors and their regulators to achieve fidelity and flexibility in lineage allocation. The transcriptional repressor Growth factor independence (GFI)-1 is comprised of conserved SNAG and zinc-finger motifs separated by a linker region poorly conserved with GFI1B, its closest homolog. Moreover, GFI1 and GFI1B coordinate distinct developmental fates in hematopoiesis, suggesting their functional differences may derive from structures within their linkers. We show a binding interface between the GFI1 linker and the SP-RING domain of PIAS3, an E3-SUMO ligase. The PIAS3 binding region in GFI1 contains a conserved type-I SUMOylation consensus element, centered on lysine-239 (K239). In silico prediction algorithms identify K239 as the only high probability site for SUMO modification. We show GFI1 is modified by SUMO at K239. SUMOylation-resistant derivatives of GFI1 fail to complement Gfi1 depletion phenotypes in zebrafish primitive erythropoiesis and granulocytic differentiation in cultured human cells. LSD1/CoREST recruitment and MYC repression by GFI1 are profoundly impaired for SUMOylation-resistant GFI1 derivatives, while enforced expression of MYC blocks granulocytic differentiation. These findings suggest that SUMOylation within the GFI1 linker favors LSD1/CoREST recruitment and MYC repression to govern hematopoietic differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping