It does not seem possible that these two processes can coexist:

1) Genetic imprinting is the phenomenon where genes are expressed differently depending on the parent of origin:

1a. Methylated stretches of DNA are not transcribed.

1b. If the gene copy originating with mom is methylated but dad's copy is not, then only dad's copy will be expressed (e.g. Prader Willi syndrome).

1c. Methylation is preserved during cell divisions.

1d. Methylation is wiped at gametogenesis, when females will erase dad's imprints and re-imprint according to maternal imprint before meiosis.

But now I'm reading about the role of epigenetics in cell differentiation, and I discover:

2) Cell differentiation occurs with lineage-specific patterns of methylation.

2a. Immediately after fertilization (prior to the first cell division), the paternal genome undergoes demethylation.

2b. The maternal genome undergoes demethylation during the first few cell divisions.

2c. Cell differentiation is accompanied and perhaps even accomplished by progressive re-methylation following these "wipes."

Source for 2): http://labs.genetics.ucla.edu/fan/papers/HuangK_RM2010.pdf "DNA methylation in cell differentiation and reprogramming: an emerging systematic view" Huang & Fan (2010). Regen Med. 5(4):531-44.

I suspect that there is no conflict and I merely misunderstand one, the other, or both. Otherwise, how can a pattern of methylation be wiped both during gametogenesis and early embryonic stages and still be inherited?


2 Answers 2


What if imprinted regions are immune to being wiped? Also, you may be confusing DNA methylation, and histone methylation (?). Classical biochemistry posits that DNA methylation states can be transmitted from a dividing mother cell to both daughter cells because after DNA replication the two daughter chromosomes will each be hemi-methylated, and a DNA methylase that finds a hemi-methylated site will methylate the other strand (like a corrective editing mechanism). The third thing to consider in your question is that parental imprinting is established in the germ line. In terms of wiping other epigenetic marks during early embryogenesis, the only ones present would be the ones involved in gametogenesis. In other words, as far as we know, genes activated in muscle development are never expressed after fertilization in the zygotic cells that will give rise to the primordial germ cells, so those muscle-specific epigenetic marks don't need to be wiped off in the embryo. Neither the sperm nor the egg ever expressed muscle myosin, etc.


Probably, there are narrow and wide definitions for imprinting. I am guessing the history of researches about imprinting would be like the followings.

Initially, maternal or paternal phenotype transmissions were recognized and some of such phenotype seemed because the maternal or paternal responsible gene does not work. As you know this is clearly imprinting.

Then, DNA methylation was discovered and turned out to be responsible for inactivation of imprinting genes defined above. However DNA methylation and repression of the expression by methylation occur to other genes, too. ES cells have distinct a DNA methylation pattern, which can probably explain the distinct gene expression pattern at least partially, I think. In addition, suppression of some tumor suppressor genes by methylation occurs during the course of carcinogenesis. It looks like DNA methylation regulates gene expressions as well as imprinting defined above. I know people call all gene regulations by DNA methylation imprinting. This is the wide definition.


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