Analysis of vertebrate SCL loci identifies conserved enhancers

Göttgens, B. Barton, L.M. Gilbert, J.G.R. Bench, A.J. Sanchez, M.J. Bahn, S. Mistry, S. Grafham, D. McMurray, A. Vaudin, M. Amaya, E. Bentley, D.R. and Green, A.R.

Nature Biotechnology 18:181-186 (2000)

ABSTRACT: 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.

© 1999 Elsevier Science Ltd

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