Epigenetic Regulation of the Autism Susceptibility Gene, ENGRAILED 2 (EN2)

2010-07

Autism Spectrum Disorder (ASD) risk is likely due to both genetic susceptibility and non-genetic environmental factors. The environment can influence gene expression by epigenetic differences. Our previous research demonstrated the homeobox transcription factors, ENGRAILED 2 (EN2) is genetically associated with ASD. The ASD-associated variant is also functional, increasing levels both in vitro and in vivo. Human post-mortem studies also demonstrate increased EN2 levels. We then hypothesized that increased levels could also be due to epigenetic changes since EN2 is fl by 6 significant CpG islands. To investigate this question we treated two human neuronal cell lines with the methylation inhibitor, AZA, and the methyl donor, SAM. AZA treated cell lines resulted in increased EN2 mRNA levels while SAM decreased express. Preliminary bisulfite sequencing indicates changes in EN2 mRNA levels are correlated with differences in DNA methylation. The same methylation differences are observed in the above post-mortem samples, suggesting epigenetic changes may also contribute to the increase of EN2 observed in these samples.
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Psychology; Genetic Engineering and Molecular Biology; GENES; ORDER DISORDER TRANSFORMATIONS; CELLS(BIOLOGY); DEOXYRIBONUCLEIC ACIDS; ENVIRONMENTS; GENETIC ENGINEERING; GENETICS; IN VITRO ANALYSIS; IN VIVO ANALYSIS; METHYL RADICALS; METHYLATION; RISK; SULFITES; AUTISM; ENGRAILED 2; EPIGENETICS; Text

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