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Introduction to Forkhead Genes 

Introduction to Forkhead Genes
Introduction to Forkhead Genes

Naoyuki Miura

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date: 25 February 2021

Finding a mutant in the organism is always a key factor for identification of a gene involved in a biological function. One Drosophila mutant which has a homeotic transformation called fork head, thus opened the way to identify the causative genes for several inherited diseases with pleiotropic phenotypes. In 1989 and 1990, two genes were identified: one, fork head was identified through fly genetics while the other, HNF-3α‎ (hepatocyte nuclear factor-3α‎) was identified by biochemical purification. A conserved region encoding 100 amino acids found in the two genes was named “forkhead” domain. More than one-hundred forkhead genes have been cloned, from yeast to humans. In November 1998, forkhead proteins were renamed Fox (Forkhead box). They act as either transcriptional activators or transcriptional repressors. Gene knockout technology has been applied in mice to this family of genes to clarify the developmental roles of each gene. Concerted, positional cloning has identified several forkhead genes as the causative genes for human and rodent inherited disorders. These results indicate that Fox genes play important roles as transcriptional regulators in cell proliferation, cell-fate determination and cell differentiation during development and also are the causative genes for human inherited disorders with pleiotropic phenotypes.

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