PUBLICATION

Cohesin-dependent regulation of Runx genes

Authors
Horsfield, J.A., Anagnostou, S.H., Hu, J.K., Cho, K.H., Geisler, R., Lieschke, G., Crosier, K.E., and Crosier, P.S.
ID
ZDB-PUB-070629-1
Date
2007
Source
Development (Cambridge, England)   134(14): 2639-2649 (Journal)
Registered Authors
Crosier, Kathy, Crosier, Phil, Geisler, Robert, Horsfield, Jules, Lieschke, Graham J.
Keywords
Runx1, Runx3, Rad21, Scc1, Cohesin
MeSH Terms
  • Chromatids/physiology
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Brain/metabolism
  • Core Binding Factor Alpha 2 Subunit/biosynthesis*
  • Nuclear Proteins/genetics
  • Nuclear Proteins/physiology*
  • Core Binding Factor Alpha 3 Subunit/biosynthesis*
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Gene Expression Regulation, Developmental
  • Animals
  • Mitosis
  • Chromosomal Proteins, Non-Histone/genetics
  • Chromosomal Proteins, Non-Histone/physiology*
  • Mutation
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/metabolism
  • Cell Differentiation
  • Blood Cells/cytology
  • Blood Cells/metabolism
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/physiology*
  • Protein Subunits/genetics
  • Protein Subunits/metabolism
  • Protein Subunits/physiology
  • Hematopoiesis
  • Zebrafish/embryology
  • Zebrafish/metabolism*
(all 28)
PubMed
17567667 Full text @ Development
Abstract
Runx transcription factors determine cell fate in many lineages. Maintaining balanced levels of Runx proteins is crucial, as deregulated expression leads to cancers and developmental disorders. We conducted a forward genetic screen in zebrafish for positive regulators of runx1 that yielded the cohesin subunit rad21. Zebrafish embryos lacking Rad21, or cohesin subunit Smc3, fail to express runx3 and lose hematopoietic runx1 expression in early embryonic development. Failure to develop differentiated blood cells in rad21 mutants is partially rescued by microinjection of runx1 mRNA. Significantly, monoallelic loss of rad21 caused a reduction in the transcription of runx1 and of the proneural genes ascl1a and ascl1b, indicating that downstream genes are sensitive to Rad21 dose. Changes in gene expression were observed in a reduced cohesin background in which cell division was able to proceed, indicating that cohesin might have a function in transcription that is separable from its mitotic role. Cohesin is a protein complex essential for sister chromatid cohesion and DNA repair that also appears to be essential for normal development through as yet unknown mechanisms. Our findings provide evidence for a novel role for cohesin in development, and indicate potential for monoallelic loss of cohesin subunits to alter gene expression.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
AB + MO2-rad21astandard conditionsPrim-15
AB + MO2-rad21astandard conditionsPrim-15
AB + MO2-rad21astandard conditionsLong-pec
AB + MO2-rad21astandard conditionsLong-pec
AB + MO2-rad21astandard conditionsLong-pec
AB + MO3-rad21astandard conditionsPrim-15
AB + MO3-rad21astandard conditionsPrim-15
AB + MO5-smc3standard conditionsLong-pec
AB + MO6-smc3standard conditionsLong-pec
AB + MO6-smc3standard conditionsLong-pec
1 - 10 of 31
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nz171
    		Point Mutation
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    rad21aMO1-rad21aMRPHLNO
    rad21aMO2-rad21aMRPHLNO
    rad21aMO3-rad21aMRPHLNO
    smc3MO3-smc3MRPHLNO
    smc3MO4-smc3MRPHLNO
    smc3MO5-smc3MRPHLNO
    smc3MO6-smc3MRPHLNO
    1 - 7 of 7
    Show
    Fish
    Fish
    AB
    AB + MO2-rad21a
    AB + MO3-rad21a
    AB + MO3-smc3
    AB + MO5-smc3
    AB + MO6-smc3
    rad21anz171/nz171 (AB)
    WT + MO3-rad21a
    1 - 8 of 8
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
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    Citation
    Horsfield, J.A., Anagnostou, S.H., Hu, J.K., Cho, K.H., Geisler, R., Lieschke, G., Crosier, K.E., and Crosier, P.S. (2007) Cohesin-dependent regulation of Runx genes. Development (Cambridge, England). 134(14):2639-2649.