Long-range comparison of human and mouse SCL loci: localized regions of sensitivity to restriction endonucleases correspond precisely with peaks of conserved noncoding sequences.
Long-range comparative sequence analysis provides a powerful strategy for identifying conserved regulatory elements. The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a pivotal role in hemopoiesis and vasculogenesis, and it displays a highly conserved expression pattern. We present here a detailed sequence comparison of 193 kb of the human SCL locus to 234 kb of the mouse SCL locus. Four new genes have been identified together with an ancient mitochondrial insertion in the human locus. The SCL gene is flanked upstream by the SIL gene and downstream by the MAP17 gene in both species, but the gene order is not collinear downstream from MAP17. To facilitate rapid identification of candidate regulatory elements, we have developed a new sequence analysis tool (SynPlot) that automates the graphical display of large-scale sequence alignments. Unlike existing programs, SynPlot can display the locus features of more than one sequence, thereby indicating the position of homology peaks relative to the structure of all sequences in the alignment. In addition, high-resolution analysis of the chromatin structure of the mouse SCL gene permitted the accurate positioning of localized zones accessible to restriction endonucleases. Zones known to be associated with functional regulatory regions were found to correspond precisely with peaks of human/mouse homology, thus demonstrating that long-range human/mouse sequence comparisons allow accurate prediction of the extent of accessible DNA associated with active regulatory regions.
Göttgens
B
B
The Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Addenbrooke's Hospital Site, Cambridge CB2 2XY, UK. bg200@cam.ac.uk
Gilbert
J G
JG
Barton
L M
LM
Grafham
D
D
Rogers
J
J
Bentley
D R
DR
Green
A R
AR
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017124:Conserved Sequence / Q000235:genetics*; D004262:DNA Restriction Enzymes / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000235:genetics; D052138:Genes, Neoplasm; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D006868:Hydrolysis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D004262:DNA Restriction Enzymes; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human