To study the methylation imprinting marks of two oppositely imprinted genes, H19 and MEST/PEG1, in human testicular spermatozoa from azoospermic patients with different etiologies.
In contrast, CTCF is the known reader and protector of Igf2/H19 imprinting marks in somatic cells [11], [12], [13], [14], [15].
It is just recently that the molecular players that protect/maintain imprinting marks during reprogramming in preimplantation embryos have been identified, in particular, an epigenetic modifier complex formed by ZFP57 and TRIM28/KAP1.
Moreover, on a more general genomic scale it has been shown that maintenance of imprinting marks in early zygotic development requires not only protection against postfertilisation demethylation, but also protection against somatic remethylation.
Loss of maternal Dnmt1o led to loss of imprinting at many loci, including paternally imprinted H19 and maternally imprinted Snrpn (Howell et al., 2001), resulting in profound phenotypic variation in the offspring expressed as a retarded development at mid gestation in 60% of the embryos owing to the deficiency in the maintenance of imprinting marks (Toppings et al., 2008).
The dissimilar gonadal environment enables sex-dependent epigenetic modifications of paternal and maternal DNA such as reactivation of the X chromosome in female germ cells [ 3, 4], inactivation of a single X chromosome in pachytene spermatocytes [ 5- 7] or differential establishment of imprinting marks on paternally or maternally imprinted genes [ 8, 9].
During preimplantation development, genomic imprinting is jeopardized by global DNA demethylation, and some actors such as the complex Zfp57/TRIM28/KAP1 are required to protect epigenetic imprinting marks [ 33 ].
Mammalian CTCF's are also involved in reading gene imprinting marks (i.e. Boris) at a high fraction of imprinted genes [ 76].
The normal imprinting marks are inherited from the parental gametes and are then maintained in the somatic cells of an individual.
Imprinting marks, like other epigenetic marks, are re-established at each generation by successive removal and re-establishment in the germ cell lineages, and then in early zygotic development.
The majority of secondary DMRs found at imprinted genes are methylated on the paternally-inherited allele, suggesting that there may be a common mechanism responsible for establishing secondary imprinting marks.
