Just like tweets about the U.S. Presidential race, updates on the function of 5-hydroxymethylcytosine (5-hmC) keep pouring in. For a while, no one really knew what the mod did, but new reports find that while some 5-hmC marks are stable, and others are dynamic, both may be critical for neural development right after birth and later on in adulthood.
Researchers at Emory, the University of Chicago, and the University of Wisconsin-Madison seemed to expand on previous 5-hmC work, including others we’ve featured in EpiGenie on embryonic stem cell (ESC) differentiation, ES cell self-renewal, and 5-hmC tissue distribution. The team employed a chemical-labeling method to scope out genomic 5-hmC locations. The technique uses β-glucosyltransferase to transfer an engineered glucose onto 5-hmC which can then be tagged with biotin. With this and several other methods, they generated detailed genome-wide epigenetic maps of 5-hmC in the mouse cerebellum and hippocampus seven days after birth, at six weeks old, and at one year old leading to lots of new insights into 5-hmC.
- Overall, 5-hmC increased over time through adulthood, but this didn’t correlate with an increase in Tet expression, unlike previously reported relationships in ESCs. (Tet proteins are known to change 5-mC to 5-hmC.)
- Some 5-hmCs were stable, while some others were dynamic.
- The genomic distributions of 5-hmC in the brain are different from those in ESCs.
- Some features of 5-hmC in mouse brain were conserved in human brains, such as 5-hmC-depleted X chromosomes and 5-hmC enrichment in intragenic regions.
- In an animal model of Rett Syndrome, a disorder in which children develop normally but then regress, the amount of 5-hmC was inversely correlated with levels of MeCP2, a protein implicated in Rett syndrome and which may prevent 5-mC from becoming 5-hmC.
- Based on their results, the researchers conclude that 5-hmC has a critical role in neural development and disease.
Follow the flow of 5-hmC updates at Nature Neuroscience, January 2012.