Oral Presentation ASPCR-ASDR Conference 2013

A novel epigenetic regulator of epidermal proliferation in specific facial zones. (#62)

Stephen J Palmer 1 , Cesar P Canales 1 , Paulina Carmona-Mora 1 , Florence Tomasetig 1 , Pritinder Kaur 2 , Ian Smyth 3 , Peter W Gunning 1 , Edna C Hardeman 1
  1. Cellular and Genetic Medicine Unit, University of New South Wales, Sydney, NSW, Australia
  2. Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  3. Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

Williams-Beuren syndrome (WBS) is a developmental disorder resulting from a hemizygous microdeletion of chromosome 7, causing a characteristic set of neurological and physical abnormalities. WBS is typified by a distinctive craniofacial appearance that involves an enlargement of specific soft tissue features such as the lips. Genotype/phenotype correlations in patients with atypical deletions suggest that the facial gestalt, maps to a pair of genes that encode the evolutionarily-related transcriptional regulators GTF2IRD1 and GTF2I.

To test these mapping data and to determine molecular cause, we have generated Gtf2ird1 knockout mouse lines, which show some similar facial features. Knockout mice show extreme thickening of the skin around the nose and lip region1 associated with an expansion of the basal proliferative zone. Concordantly, expression of Gtf2ird1 is localised to a similar zone but only during development. During adulthood, expression declines.

Our studies on the molecular function of GTF2IRD1 show that it is part of a larger gene silencing complex that lays down epigenetic marks during development. In the epidermis, it seems that these marks permanently set the epidermal proliferation rate in specific facial zones.

  1. Howard ML, Palmer SJ, Taylor KM, Arthurson GJ, Spitzer MW, Du X, Pang TY, Renoir T, Hardeman EC, Hannan AJ.(2012) Mutation of Gtf2ird1 from the Williams-Beuren syndrome critical region results in facial dysplasia, motor dysfunction, and altered vocalisations.Neurobiol Dis. 45(3)913-22