Transgenerational Epigenetic Inheritance is one of our favorite topics, it’s done a great job of showing old school Mendelian inheritance who’s boss by creating the molecular complexity of complex traits. With phenotypes and exposures aplenty, the one thing that has been missing is catching the inheritance of an acquired epigenetic mark in the act. And that’s just what a team from UC Santa Cruz did by tracing the intimate dance of the inheritance of H3K27me via the Polycomb repressive complex 2 (PRC2).
By looking at C. elegans germ cells they discovered a mechanism of transgenerational epigenetic inheritance, here’s how it goes down:
- PRC2 represses the X-chromosome in germ cells via H3K27me, which is transmitted to a future embryo by the sperm and oocytes of it’s parents.
- They created embryos without PRC2, which allowed for worms with chromosomes either containing and/or missing H3K27me.
- Using this they showed that H3K27me is transmitted to daughter chromatids during multiple cell divisions, but (without PRC2) the signal fades over generations.
- They then mated the PRC2 null worms with some wild types, creating children with variable chromosome methylation and a functioning PRC2, and observed that the unique mosaic patterns inherited from the null parent persist through embryogenesis and are present in the progeny.
- Not only are the marks transmitted, but with PRC2 they are also maintained and the signal does not fade, suggesting that PRC2 is replenishing H3K27me across cell divisions.
These results provide a concrete example of histones and their enzymes creating transgenerational epigenetic inheritance. Senior author Susan Strome shares that “Transgenerational epigenetic inheritance is not a solved field—it’s very much in flux. There are dozens of potential epigenetic markers. In studies that document parent-to-child epigenetic inheritance, it’s not clear what’s being passed on, and understanding it molecularly is very complicated. We have a specific example of epigenetic memory that is passed on, and we can see it in the microscope. It’s one piece of the puzzle.”
Learn how you can find the rest of the puzzle pieces in Science, September 2014