Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression
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.
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Footnotes
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↵3 Corresponding author.
↵3 E-MAIL weinmann{at}u.washington.edu; FAX (206) 543-1013.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1689708.
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- Received April 29, 2008.
- Accepted September 8, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press