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

FOXP2基因的最新发现为语言学和分子遗传学的结合提供了一个新的研究领域。FOXP2基因是FOX家族的一个转录因子，在人类特异性语言障碍家族中有突变的报道。在从灵长类谱系到人类的进化过程中，FOXP2基因发生了两个氨基酸的变化。我们尝试用微阵列技术鉴定人类和黑猩猩FOXP2的靶基因。我们采用了flip-in重组酶和Tet ON/OFF系统来减少转染伪影。与人类Tet ON和Tet OFF条件下的表达谱相比，1671个基因表达发生了显著变化，其中641个基因表达上调，1030个基因表达下调。与黑猩猩Tet ON和Tet OFF条件下的表达谱相比，1562个基因的表达发生了显著变化，其中794个基因表达上调，768个基因表达下调。此外，与人类和黑猩猩Tet ON条件的表达谱相比，2836个基因的表达发生了显著变化，1433个基因表达上调，1403个基因表达下调。我们的研究结果表明，在人类和黑猩猩的FOXP2转录因子中，一些靶基因是共同的，但有些是不同的。将我们在Tet ON/OFF系统中的数据与之前通过微量分析和ChIP-on-chip分析获得的数据进行比较，表明有7个基因（基因名称直到我们的论文被接受才显示）明显是人类FOXP2基因的靶标。对这些受影响的基因进行更详细的分析，有助于阐明人类语言习得的大脑发育机制和人类语言障碍的遗传诊断。

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.