The central dogma has taken quite a beating thanks to epigenetics rule-bending ways. With all the cross talk and looping going on it’s hard to tell who’s the boss these days.
In their recent review, Mahajan and Mahajan from the Moffit Cancer Centre in Florida discuss the implications of their latest finding (Nature Structural & Molecular Biology, August 2012) : histones regulating histones.
To sum up their findings, Dr. Mahajan said that the research “shows for the first time that WEE1 kinase, primarily known for its cell cycle regulation function, also possess epigenetic modulator activity.” Mahajan went on to say “WEE1 deposits repressive epigenetic marks specifically upstream of Histone gene cluster suppressing histone synthesis to maintain precise equimolar ratio of DNA with histones.”
The principles presented in this review are pretty far-reaching, and the hard-core cell biologists out there will certainly appreciate the intricate details. Here some key take home messages:
- In terms of pure epigenetics, this is a solid example of “histones regulating histones.” It opens up a whole new world in the regulation of gene expression.
- From a cell biology perspective this research ultimately provides a novel, direct link between epigenetics and cell-cycle progression” through the “dual role for WEE1 as both a mitotic gatekeeper and a surveyor of chromatin synthesis”.
Dr. Mahajan shared with us that this finding “was purely serendipitous. Both identification of novel histone tyrosine phosphorylation event (pY37-H2B) and its role in regulation of histone synthesis by negatively regulating transcription at the end of S phase was a complete surprise. We were neither looking for it nor expecting it.”
Enjoy the serendipitous details in Trends in Genetics, July 2013.