Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression (original) (raw)

  1. Sara A. Miller1,2,
  2. Albert C. Huang1,2,
  3. Michael M. Miazgowicz2,
  4. Margaret M. Brassil2, and
  5. Amy S. Weinmann2,3
  6. 1 Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195, USA;
  7. 2 Department of Immunology, University of Washington, Seattle, Washington 98195, USA

Abstract

During cellular differentiation, both permissive and repressive epigenetic modifications must be negotiated to create cell-type-specific gene expression patterns. The T-box transcription factor family is important in numerous developmental systems ranging from embryogenesis to the differentiation of adult tissues. By analyzing point mutations in conserved sequences in the T-box DNA-binding domain, we found that two overlapping, but physically separable regions are required for the physical and functional interaction with H3K27-demethylase and H3K4-methyltransferase activities. Importantly, the ability to associate with these histone-modifying complexes is a conserved function for the T-box family. These novel mechanisms for T-box-mediated epigenetic regulation are essential, because point mutations that disrupt these interactions are found in a diverse array of human developmental genetic diseases.

Footnotes