An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

How do epigenetics bypass reprogamming on imprinted genes?

Well, it depends on which "reprogramming" you think. There are two waves of reprogramming occurring in mammals: one in the precursors of the future oocytes and spermatozoa (germline reprogramming) and one again after fertilization (early embryo reprogrammming).  I think this is this second wave you are refering to. By definition, imprinted genes acquire their DNA methylation in a sex-specific manner, in the oocyte and  in the sperm. Then indeed, while the rest of the genome is subject to a wave of DNA demethylation after fertilization, as part of the "rebooting" of the embryonic genome, imprinted genes have this special ability to maintain their parent-specific DNA methylation in the embryo. The underlying mechanism has been recently revealed, and was quite a surprise for the imprinting community! The protection of the imprinted genes is embedded in their sequence… meaning that this protection is genetically determined. They carry indeed multiple motifs of 6 to 7 nucleotides (TGCCGC exactly), which will recruit a specific protein called ZFP57 only when this motif is methylated. ZFP57 itself is part of a protein complex, which somehow keeps the DNA methyltransferases around these motifs. So while the imprinted genes keep on being continuously methylated in the embryo because the DNA methyltransferase enzymes are attached to them,  the other sequences of the genome will lose their methylation.
However, this mode of protection does not apply to the germline reprogramming period: as the rest of the genome, the imprinted genes will lose their DNA methylation in this context… and this is actually crucial, as you need now to re-establish methylation in your germline according to your sex. Meaning that females will acquire in their oocytes methylation marks reflecting their maternal status (maternal imprinting), while males will acquire paternal-specific DNA methylation marks (paternal imprinting) in their spermatozoa. And the loop is closed.

answered by: Deborah Bourc'his