Transcriptional regulation of the stem cell leukemia gene (SCL)--comparative analysis of five vertebrate SCL loci.
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 of SCL 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 mouse SCL 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 of SCL transcription.
Göttgens
Berthold
B
Cambridge Institute for Medical Research, Cambridge University, Cambridge, CB2 2XY, United Kingdom. bg200@cam.ac.uk
Barton
Linda M
LM
Chapman
Michael A
MA
Sinclair
Angus M
AM
Knudsen
Bjarne
B
Grafham
Darren
D
Gilbert
James G R
JG
Rogers
Jane
J
Bentley
David R
DR
Green
Anthony R
AR
D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D002645:Chickens; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011061:Poly A / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D023721:Tetraodontiformes; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins
D020121:5' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011061:Poly A; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489366:Tal1 protein, mouse; C489367:tal1 protein, zebrafish; C067143:TAL1 protein, human