Writing in the Journal of the Federation of American Societies for Experimental Biology under the title “The Complex of TFII-I, PARP1, and SFPQ Proteins Regulates the DYX1C1 Gene Implicated in Neuronal Migration and Dyslexia,” Isabel Tapia-Páez and colleagues revealed that they have discovered a group of proteins that apparently act together to control the transcription of DNA (deoxyribonucleic acid that forms genetic material) code into RNA (ribonucleic acid which controls synthesis of proteins) code. Although the gene DYX1C1 has been implicated in only a small proportion of cases of dyslexia, it is important in general because the finding moves researchers closer to understanding how genes can influence behavior as complex as reading.
DYX1C1 was first identified as a candidate gene for dyslexia susceptibility, and its role in controlling neuronal migration during embryogenesis and effect on learning in rodents have been verified. In contrast, genetic association studies have been ambiguous in replicating its effects on dyslexia. To better understand the regulation of DYX1C1 and the possible functional role of genetic variation in the promoter of DYX1C1, we selected three single-nucleotide polymorphisms (SNPs) with predicted functional consequences or suggested associations to dyslexia for detailed study. Electrophoretic mobility shift assays suggested the allele-specific binding of the transcription factors TFII-I (to rs3743205) and Sp1 (to rs16787 and rs12899331) that could be verified by competition assays. In addition, we purified a complex of protein factors binding to the previously suggested dyslexia-related SNP, –3G/A (rs3743205). Three proteins, TFII-I, PARP1, and SFPQ, were unambiguously identified by mass spectrometry and protein sequencing. Two SNPs, rs16787 and rs3743205, showed significant allelic differences in luciferase assays. Our results show that TFII-I, PARP1, and SFPQ proteins, each previously implicated in gene regulation, form a complex controlling transcription of DYX1C1. Furthermore, allelic differences in the promoter or 5′ untranslated region of DYX1C1 may affect factor binding and thus regulation of the gene.
Tapia-Páez, I., Tammimies, K., Massinen, S., Roy. A. L., Kere, J. (2008). The complex of TFII-I, PARP1, and SFPQ proteins regulates the DYX1C1 gene implicated in neuronal migration and dyslexia. The FASEB Journal, 22, 3001-3009.
Link to the page from which I grabbed the abstract; if you visit it from an institution that has an agreement with the publisher, you will be able to download a PDF of the full paper. Previous related content from LD Blog, see 1 Nov 2005 and 3 Mar 2008.