2018/08/20

Transgenerational Epigenetic Inheritance - Epigenetic Marks to Phenotype

Differentiation in Embryonic Cells: Linking Histone Acetylation and DNA Methylation to a Heritable Phenotype

Excerpt: "Although the mechanisms of how histone marks such as acetyl tags are maintained are still to be determined, it has been shown that these acetyl tags can in fact be transmitted through sex gametes and cause a heritable phenotype in the growing embryonic cells. For example in Study 2, acetyl tags were seen at the BDNF promoters in the sperm of the cocaine-sired fathers as well as in the male progeny. Another example is shown below.

In the Study by van der Heijden et al, they used DAPI (to stain the nucleus) and specific antibodies for staining acetylated lysine 8 on histone 4 (in green) to show that after fertilization of egg and sperm, acetyl tags are seen in the zygote that were passed on from the sperm of the fathers. The figure above shows their results, with the sperm pronucleus in panel A and the eventual spreading of the acetyl tags once the nucleus begins to decondense.

These acetyl tags, passed on through sperm, have then been shown to create heritable phenotypes in the resulting progeny. As seen in the second major study highlighted on this site, the acetyl tags were maintained and they increased expression of specific genes. Acetyl tags are also known to be able to shut genes down by recruiting molecular machinery to modify the nucleosome. One such pathway includes the shutting off of the Oct4 pluripotency gene in differentiating embryonic cells, so that reprogramming may be shut down. 




Here acetyl tags recruit G9a (a methyltransferase) and HDACs and allow for the deacetylation and demethylation of the histones. G9a will then methylate K9 of histone 3, which then attracts histone methyl-binding proteins such as HP1. These recruit DNMTs to methylate the DNA, shutting off the gene. Other genes have been shown to be shut down in a similar pathway during early embryonic development."

My comment: This is how transgenerational epigenetic inheritance works. This is why genetically (DNA) identical twins might have different colors of skin, eyes and hair. These histone epigenetic markers are mediated by non coding RNA molecules during early stages of embryonic development. Histone code is a biological database that is able to store most of organisms' traits (phenotype). Any change in organisms is due to epigenetic regulation of existing biological information or gradual but inevitable disappearance of information. That's why there's no mechanism for evolution. Don't get lost.