Analysis of vertebrate SCL loci identifies conserved enhancers.
The SCL gene encodes a highly conserved bHLH transcription factor with a pivotal role in hemopoiesis and vasculogenesis. We have sequenced and analyzed 320 kb of genomic DNA composing the SCL loci from human, mouse, and chicken. Long-range sequence comparisons demonstrated multiple peaks of human/mouse homology, a subset of which corresponded precisely with known SCL enhancers. Comparisons between mammalian and chicken sequences identified some, but not all, SCL enhancers. Moreover, one peak of human/mouse homology (+23 region), which did not correspond to a known enhancer, showed significant homology to an analogous region of the chicken SCL locus. A transgenic Xenopus reporter assay was established and demonstrated that the +23 region contained a new neural enhancer. This combination of long-range comparative sequence analysis with a high-throughput transgenic bioassay provides a powerful strategy for identifying and characterizing developmentally important enhancers.
Göttgens
B
B
University of Cambridge, Department of Haematology, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.
Barton
L M
LM
Gilbert
J G
JG
Bench
A J
AJ
Sanchez
M J
MJ
Bahn
S
S
Mistry
S
S
Grafham
D
D
McMurray
A
A
Vaudin
M
M
Amaya
E
E
Bentley
D R
DR
Green
A R
AR
Sinclair
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002645:Chickens; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins; D012249:Rhombencephalon / Q000196:embryology; D017386:Sequence Homology, Amino Acid; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics*; D014981:Xenopus; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D029867:Xenopus Proteins; C489365:TAL1 protein, Xenopus; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human