Sonic hedgehog signaling affected by promoter hypermethylation induces aberrant Gli2 expression in Spina bifida

International Conference and Exhibition on Molecular Medicine and Diagnostics

August 24-26, 2015 London, UK

Xiaolin Lu

Posters-Accepted Abstracts: J Mol Genet Med

Abstract :

GLI2 is a key mediator of the Sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development
during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this
study, we compared the methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the
underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was distributed significantly
differently between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied
by aberrant GLI2 expression. Moreover, a significant negative correlation was found between the folate level of brain tissue and
the gli2 methylation status (r=−0.41, P=0.014), while gli2 hypermethylation increased the risk of spina bifida with an odds ratio of
12.45 (95% confidence interval: 2.71–57.22, P=0.001). We also used a cell model to illustrate the effect of gli2 expression and the
accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2
hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional
factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have less expression along with
decreased expression of gli2 in the cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which
was affected by the change in chromatin status and the capacity of transcription factor binding.

Biography :

Xiaolin Lu has completed her MM at the Capital Institute of Pediatrics in 2007, and became a young researcher at Beijing Municipal Key Laboratory of Child Development
and Nutriomics, Capital Institute of Pediatrics.The main work of her research is about the interaction of genetics and epigenetics in the mechanism of birth defects. Since
2013, she has published about 2 articles on genetic and epigenetic alternations in birth defects as the first author and joint first author.