Wednesday, May 25, 2016

Histone modification upstream of DNA methylation?

We know that DNA methylation patterns are the best predictors of chronological age.
http://www.nature.com/news/biomarkers-and-ageing-the-clock-watcher-1.15014
In this study:
Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging
age dependent lactose intolerance is  investigated.
Lactase enzyme DNA is downregulated in mouse by day 60 and in humans by the second decade of life.
This is achived by increased methylation of the lactase gene DNA.
However there are populations that do not show age related loss of lactose tolerance. DNA of lactase does not get methylated by age in these individuals. The article points to H3K4me1 and H3K27ac histone modifications in the differentially methylated regions. In these regions age related methylation is overcome in lactose tolerant individuals. The  epigenetic clock is selectively stopped here.

Another article also underpins the role of histone modifications in DNA methylation patterns
Molecular coupling of DNA methylation and histone methylation

" DNA methylation is associated with the absence of H3K4 methylation (H3K4me0) and the presence of H3K9 methylation, but has little correlation with methylation of H3K2"

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