Sp5, a new member of the Sp1 family, is dynamically expressed during development and genetically interacts with Brachyury.
We describe the identification, biochemical characterisation, and mutation of a novel mouse gene: Sp5. Sp5 encodes a protein having a C-terminal C(2)H(2) zinc finger domain closely related to that of the transcription factor Sp1. In vitro, DNA binding studies show that it binds to the GC box, a DNA motif present in the promoter of a very large number of genes, including Brachyury, and recognised by members of the Sp1 family. However, outside of its DNA binding domain, Sp5 has little homology with any other member of the Sp1 family. In contrast to the ubiquitous expression of Sp1, Sp5 exhibits a remarkably dynamic pattern of expression throughout early development. This is suggestive of a role in numerous tissue patterning events, including gastrulation and axial elongation; differentiation and patterning of the neural tube, pharyngeal region, and somites; and formation of skeletal muscle in the body and limbs. Mice homozygous for a targeted mutation in Sp5 show no overt phenotype. However, the enhancement of the T/+ phenotype in compound mutant mice (Sp5(lacZ)/Sp5(lacZ), T/+) indicates a genetic interaction between Sp5 and Brachyury. These observations are consistent with a role for Sp5 in the coordination of changes in transcription required to generate pattern in the developing embryo.
Harrison
S M
SM
Division of Mammalian Development, The National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.
Houzelstein
D
D
Dunwoodie
S L
SL
Beddington
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005326:Fetal Proteins; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010614:Pharynx / Q000196:embryology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019170:Somites / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics*; D014157:Transcription Factors; D016335:Zinc Fingers / Q000235:genetics; D000098908:Brachyury Protein
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D016329:Sp1 Transcription Factor; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C417217:Sp5 protein, mouse