A Long Polymorphic GT Microsatellite within a Gene Promoter Mediates Non-Imprinted Allele-Specific DNA Methylation of a CpG Island in a Goldfish Inter-Strain Hybrid

Abstract

It is now widely accepted that allele-specific DNA methylation (ASM) commonly occurs at non-imprinted loci. Most of the non-imprinted ASM regions observed both within and outside of the CpG island show a strong correlation with DNA polymorphisms. However, what polymorphic cis-acting elements mediate non-imprinted ASM of the CpG island remains unclear. In this study, we investigated the impact of polymorphic GT microsatellites within the gene promoter on non-imprinted ASM of the local CpG island in goldfish. We generated various goldfish heterozygotes, in which the length of GT microsatellites or some non-repetitive sequences in the promoter of no tail alleles was different. By examining the methylation status of the downstream CpG island in these heterozygotes, we found that polymorphisms of a long GT microsatellite can lead to the ASM of the downstream CpG island during oogenesis and embryogenesis, polymorphisms of short GT microsatellites and non-repetitive sequences in the promoter exhibited no significant effect on the methylation of the CpG island. We also observed that the ASM of the CpG island was associated with allele-specific expression in heterozygous embryos. These results suggest that a long polymorphic GT microsatellite within a gene promoter mediates non-imprinted ASM of the local CpG island in a goldfish inter-strain hybrid.

Comparative Analysis of TG/CA Repeats in Sixteen Primate Genomes Reveals the Dynamics and Role of TG/CA Repeats in the Human Genome

“…TG/CA microsatellites are the most abundant dinucleotide repeats in the human genome [4,8,12]. They exhibit multifaceted functional roles, such as modulation of gene expression [26], recombination [11] and intron splicing due to their polymorphic nature [27]. Therefore, a comparative study of these repeats in primate genomes, which originated from a common ancestor, is likely to provide useful insights into their conservation and evolution.…”

“…The copyright holder for this preprint (which this version posted May 9, 2023. ; https://doi.org/10.1101/2023.05.09.539941 doi: bioRxiv preprint showed that long polymorphic TG repeats can alter methylation of downstream CpG island in goldfish models [26]. (TG/CA) repeats also play a role in intron splicing as shown by a study conducted by Hui et al, where they showed that length of CA repeats can alter splicing efficiency by serving as HnRNP L recruitment site during intron splicing in eNOS gene [27].…”