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

2008; Cold Spring Harbor Laboratory Press; Volume: 22; Issue: 21 Linguagem: Inglês

10.1101/gad.1689708

1549-5477

Sara A. Miller, Albert C. Huang, Michael M. Miazgowicz, Margaret M. Brassil, Amy S. Weinmann,

Genetics and Neurodevelopmental Disorders

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.