Human Genetics

, Volume 107, Issue 1, pp 1–6

Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3

  • S. Brian Potterf
  • Minao Furumura
  • Karen J. Dunn
  • Heinz Arnheiter
  • William J. Pavan
Rapid Communication

DOI: 10.1007/s004390000328

Cite this article as:
Potterf, S., Furumura, M., Dunn, K. et al. Hum Genet (2000) 107: 1. doi:10.1007/s004390000328

Abstract.

Waardenburg syndrome (WS) is associated with neural crest-derived melanocyte deficiency caused by mutations in either one of three transcription factors: MITF, PAX3, and SOX10. However, the hierarchical relationship of these transcription factors is largely unknown. We show that SOX10 is capable of transactivating the MITF promoter 100-fold, and that this transactivation is further stimulated by PAX3. Promoter deletion and mutational analyses indicate that SOX10 can activate MITF expression through binding to a region that is evolutionarily conserved between the mouse and human MITF promoters. A SOX10 mutant that models C-terminal truncations in WS can reduce wild-type SOX10 induction of MITF, suggesting these mutations may act in a dominant-negative fashion. Our data support a model in which the hypopigmentation in WS, of which these factors have been implicated, results from a disruption in function of the central melanocyte transcription factor MITF.

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • S. Brian Potterf
    • 1
  • Minao Furumura
    • 2
  • Karen J. Dunn
    • 1
  • Heinz Arnheiter
    • 3
  • William J. Pavan
    • 1
  1. 1.Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC4472, Bethesda, MD 20892-4472, USA
  2. 2.Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA
  3. 3.Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA