Identification of target genes for the language-related FOXP2 transcription factor

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Recent findings of the FOXP2 gene provide a new research field combined linguistic studies and molecular genetics. Mutations of the FOXP2 gene, a FOX family transcription factor, have been reported in families of specific language impairment in human. Two amino acid changes occurred in the FOXP2 genes during evolution from primate lineages to human being. We tried to identify the target genes of the human and chimpanzee FOXP2 with microarray techniques. We adapted the flip-in recombinase and Tet ON/OFF systems to minimize transfection artifacts. Significant expression changes were found in 1,671 genes, in which 641 genes were up-regulated and 1,030 genes were down-regulated comparing with the expression profiles of human Tet ON and Tet OFF conditions. Significant expression changes were found in 1,562 genes, in which 794 genes were up-regulated and 768 genes were down-regulated, comparing with the expression profiles of chimpanzee Tet ON and Tet OFF conditions. Furthermore, significant expression changes were found in 2,836 genes, 1,433genes were up-regulated and 1,403 genes were down regulated, comparing with the expression profiles of human Tet ON and chimpanzee Tet ON conditions. Our results showed some target genes are common but some are different between the human and chimpanzee FOXP2 transcription factors. Comparing of our data in Tet ON/OFF system with previous data obtained from a microassay analysis and a ChIP-on-chip analysis, it is suggested that seven genes (genes names are not shown till acceptance of our paper) are clearly targets of the human FOXP2 genes. More detail analyses of these affected genes could contribute elucidation for the mechanism of human brain development for language acquisition and genetic diagnosis of human language disorders.