PUBLICATION
Specification of hematopoietic and vascular development by the bHLH transcription factor SCL without direct DNA binding
- Authors
- Porcher, C., Liao, E.C., Fujiwara, Y., Zon, L.I., and Orkin, S.H.
- ID
- ZDB-PUB-991103-11
- Date
- 1999
- Source
- Development (Cambridge, England) 126(20): 4603-4615 (Journal)
- Registered Authors
- Liao, Eric, Zon, Leonard I.
- Keywords
- SCL/tal-1; bHLH transcription factor; hematopoiesis; vasculogenesis; phenotypic rescue; zebrafish mutant; cloche
- MeSH Terms
-
- Base Sequence
- Erythropoiesis/genetics
- Erythropoiesis/physiology
- Mutation
- In Situ Hybridization
- Gene Expression Regulation, Developmental
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/physiology*
- Proto-Oncogene Proteins*
- Blood Vessels/embryology*
- Gene Targeting
- Hematopoiesis/genetics*
- Hematopoiesis/physiology*
- Transcription Factors/genetics*
- Transcription Factors/physiology*
- Humans
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- DNA Primers/genetics
- Leukemia/etiology
- Leukemia/genetics
- Helix-Loop-Helix Motifs/genetics
- Helix-Loop-Helix Motifs/physiology
- DNA/genetics
- DNA/metabolism
- Basic Helix-Loop-Helix Transcription Factors
- Zebrafish Proteins*
- Animals
- PubMed
- 10498694 Full text @ Development
Citation
Porcher, C., Liao, E.C., Fujiwara, Y., Zon, L.I., and Orkin, S.H. (1999) Specification of hematopoietic and vascular development by the bHLH transcription factor SCL without direct DNA binding. Development (Cambridge, England). 126(20):4603-4615.
Abstract
Transcription factors, such as those of the basic-helix-loop-helix (bHLH) and homeodomain classes, are primary regulators of cell fate decisions and differentiation. It is considered axiomatic that they control their respective developmental programs via direct binding to cognate DNA sequences in critical targets genes. Here we test this widely held paradigm by in vivo functional assay of the leukemia oncoprotein SCL, a bHLH factor that resembles myogenic and neurogenic proteins and is essential for both hematopoietic and vascular development in vertebrates. Contrary to all expectation, we find that SCL variants unable to bind DNA rescue
hematopoiesis from gene-targeted SCL(-)(/)(-) embryonic stem cells and complement hematopoietic and vascular deficits in the zebrafish mutant cloche. Our findings establish DNA-binding-independent functions of SCL critical for transcriptional specification, and should encourage reassessment of presumed requirements for direct DNA binding by other transcription factors during initiation of developmental programs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping