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Transcriptional Regulation of the Stem Cell Leukemia Gene (SCL) — Comparative Analysis of Five Vertebrate SCL Loci

  1. Berthold Göttgens1,4,5,
  2. Linda M. Barton1,4,
  3. Michael A. Chapman1,
  4. Angus M. Sinclair1,
  5. Bjarne Knudsen2,
  6. Darren Grafham3,
  7. James G.R. Gilbert3,
  8. Jane Rogers3,
  9. David R. Bentley3, and
  10. Anthony R. Green1
  1. 1Cambridge Institute for Medical Research, Cambridge University, Cambridge, CB2 2XY, United Kingdom; 2Bioinformatics Research Center, University of Aarhus, DK-8000 Denmark; 3The Wellcome Trust Sanger Institute, Cambridge, CB101SA United Kingdom

Abstract

The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a pivotal role in hematopoiesis and vasculogenesis and a pattern of expression that is highly conserved between mammals and zebrafish. Here we report the isolation and characterization of the zebrafish SCL locus together with the identification of three neighboring genes, IER5,MAP17, and MUPP1. This region spans 68 kb and comprises the longest zebrafish genomic sequence currently available for comparison with mammalian, chicken, and pufferfish sequences. Our data show conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus suggesting the likely genomic domain necessary for the conserved pattern ofSCL expression. Long-range comparative sequence analysis/phylogenetic footprinting was used to identify noncoding conserved sequences representing candidate transcriptional regulatory elements. The SCL promoter/enhancer, exon 1, and the poly(A) region were highly conserved, but no homology to other known mouseSCL enhancers was detected in the zebrafish sequence. A combined homology/structure analysis of the poly(A) region predicted consistent structural features, suggesting a conserved functional role in mRNA regulation. Analysis of the SCL promoter/enhancer revealed five motifs, which were conserved from zebrafish to mammals, and each of which is essential for the appropriate pattern or level ofSCL transcription.

[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: N. Tanese.]

Footnotes

  • ↵4 These authors contributed equally to this work.

  • ↵5 Corresponding author.

  • E-MAIL bg200{at}cam.ac.uk; FAX 44-1223-762670.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.45502.

    • Received January 4, 2001.
    • Accepted March 19, 2002.