Analysis of vertebrate SCL loci identifies conserved enhancers.

Gottgens B, Barton LM, Gilbert JG, Bench AJ, Sanchez MJ, Bahn S, Mistry S, Grafham D,

McMurray A, Vaudin M, Amaya E, Bentley DR, Green AR

Nature Biotechnology 18:181-6 (2000) Full Article (680K)

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.

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