An essential interaction between T-box proteins and histone-modifying enzymes.
Cellular differentiation requires precisely coordinated events to induce developmentally appropriate gene expression profiles. Lineage-defining transcription factors are responsible for establishing cell-type specific gene expression patterns during development. Recently, we reported a novel mechanism by which the T-box transcription factor T-bet interacts with JMJD3, an H3K27-demethylase, and Set7/9, an H3K4-methyltransferase (Genes Dev. 2008. 22: 2980-2993). Importantly, separable contact points in the T-box DNA binding domain mediate these interactions. Due to the highly conserved nature of the contact residues, these represent common interactions for the T-box family. Therefore, studies examining the molecular mechanisms that account for the ability of T-bet to regulate Ifng and Cxcr3, prototypic CD4+ Th1 genes, have provided novel insight into essential regulatory events that occur at diverse developmental transitions. In this article, we discuss the implications for these findings as well as explore the role epigenetic mechanisms may play in the development of human genetic diseases that are caused by T-box mutations, including congenital heart defects, cleft palate, pituitary deficiencies, and Ulnar-mammary syndrome.
Miller
Sara A
SA
Molecular and Cellular Biology Program, Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Weinmann
Amy S
AS
D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D020825:T-Box Domain Proteins / Q000378:metabolism*
D006657:Histones; D020825:T-Box Domain Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; D010089:Oxidoreductases, N-Demethylating; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human