Oocyte growth‐dependent progression of maternal imprinting in mice

Abstract

In mammals, some genes categorized as imprinted genes are exclusively expressed either from maternal or paternal allele. This parental-origin-specific gene expression is regulated by epigenetic modification of DNA methylation in differentially methylated region (DMR), which is independently imposed during oogenesis and spermatogenesis. It is known that methylation of DMR in the female germ line is established during oocyte growth phase. However, the cause of the progression of methylation on DMR, due to either aging of mice or growth-size of oocyte was unclear up to now. Here, we analyzed the methylation of DMR for each eight imprinted genes ( Igf2r , Lit1 , Zac1 , Snrpn , Peg1/Mest , Impact , Meg1/Grb10 , and H19 ) by bisulfite sequencing methylation assay, using oocytes from 10 dpp (days post partum), 15 dpp, 20 dpp, and adult mice. To find whether the size of oocytes is the cause of methylation, above oocytes were classified into seven groups (each oocyte diameter ranging from 40 to 75 µ µ µ µ m with intervals of 5 µ µ µ µ m). The results from juvenile mice oocytes showed that DMR methylation progressed according to oocyte growth each imprinted gene. More than 85% of DMR methylation was achieved for both Igf2r , Zac1 & Lit1 with oocyte size of reaching 55 µ µ µ µ m and Snrpn , Peg1/Mest , Impact , and Meg1/Grb10 with oocyte size of reaching 60 µ µ µ µ m. Preferential methylation of maternal allele was observed in Zac1 and Peg1/Mest of juvenile oocytes and in Snrpn of juvenile and adult oocytes. The oocyte size-dependent-methylation progressed equally for all three different-age juvenile mice. The size-dependent-methylation was also recognized in the growing oocytes collected from adult mice, although the progress is slightly slower than that of juvenile mice. From these results, we concluded that DNA methylation is established with oocyte size dependent manner, not with aging of mice.

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

“…The report suggested that imprinting anomalies can affect more than one imprinted locus and may alter the clinical presentation of imprinted disease. The results from juvenile mice oocytes showed that progression of DMR methylation for each imprinted gene examined, including Zac1/Lot1 and Lit1, was dependent on oocyte growth or size (Hiura et al, 2006). Similarly, it was found that DNA methylation of PLAGL1/LOT1/ZAC1 and HYMAI is established during the growth phase of oogenesis, which coincides with monoallelic expression from the ICR or the DMR (Arima and Wake, 2006).…”

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

“…Maternal-specific de novo DNA methylation occurs in postnatal growing oocytes, [56][57][58] and methylation acquisition is related to oocyte size. 57,58 DNA methyltransferases A (DNMT3A) and its cofactor DNA methyltransferases L (DNMT3L) are required to establish DNA methylation in growing oocytes. 59 Maternalspecific de novo DNA methylation likely contributes to gene regulation in the oocyte and marks specific genes for activity in the embryo, as in the case of imprinted genes.…”

DNA Methylation, Histone Modifications and Behaviour of AKAP95 during Mouse Oocyte Growth and Upon Nuclear Transfer of Foreign Chromatin into Fully Grown Prophase Oocytes

“…It is commonly accepted that reprogramming of oocyte chromatin involves a set of epigenetic modifications. Examination of the pattern of DNA methylation in specific sequences indeed proved that genomic imprinting, a process contrib-uting to reprogramming, takes place during oocyte growth (OBATA & KONO 2002;HIURA et al 2006). Other study reported that methylation and acetylation of histones as well as the level of global DNA methylation changes during oocyte growth in mice (KAGEYAMA et al 2007).…”