DNA methylation modulates H19 and IGF2 expression in porcine female eye

Dongxu Wang,Hao Yang,Guodong Wang,Chao Lin,Yuning Song,Zhanjun Li,Cuie Li,Dianfeng Liu,Xiaolan Li,Haibo Liu

doi:10.1590/1678-4685-gmb-2016-0194

Abstract

The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

Highlights

The imprinted gene IGF2 has been reported to be paternally expressed and it is a growth factor in mammals (Barlow et al, 1991)
The IGF2 DMR1 moves to an active domain, while IGF2 DMR2 moves to an inactive domain on the maternal allele
When the IGF2 DMR2 and DMR1 both move to an active domain on the paternal allele, H19 differentially methylated regions (DMRs) interacts with IGF2 DMR2

Summary

Introduction

The imprinted gene IGF2 has been reported to be paternally expressed and it is a growth factor in mammals (Barlow et al, 1991). Numerous studies have demonstrated that the parentspecific expression of H19/IGF2 depends on differentially methylated regions (DMRs) (Park et al, 2011; Thorvaldsen et al, 2006). Studies have shown that DMRs play an important role in the regulation of gene expression in the H19/IGF2 cluster within promoters and enhancers (Braunschweig et al, 2011). Through CTCF binding to the DMRs, IGF2 is inactivated and maternal H19 is expressed. When that binding is prevented, paternal IGF2 is expressed. This is known as parent-specific chromatin loops (Wei et al, 2005), and, as part of this mechanism, IGF2 DMRs are considered an epigenetic switch that regulates H19 and IGF2 expressions

Methods

Results

Conclusion