Just as “identical” twins can sometimes have a few noticeable differences (one has a mole on her cheek, the other doesn’t), alleles that are copies of the same gene also can be different. Allele-specific methylation (ASM) might get all the attention, but now researchers in the U.K. say that allele-specific histone modification (ASHM) might be even more important, especially at disease loci.
In the first systematic investigation of genomic ASHM in human embryonic stem cells (hESCs), the researchers made some very interesting discoveries. Here are a few of them:
- Using data from huge international sequencing projects, they identified 51 ASHM sites in H1 hESCs that clustered into six different patterns.
- ASHM and allele-specific expression co-localized in many genomic regions.
- Although ASM is often thought of as an indication of imprinting, ASHM was actually more closely associated with imprinting. So ASHM might be a better indication of imprinting, if you’re searching for that kind of thing.
- After stringent filtering of the data, seven ASHM sites were close to regions known to be deleted in disease. These were in locations associated with developmental disorders.
- Fetal lung fibroblast-derived cells didn’t show this type of ASHM-developmental disease association, so it may be specific to H1 hESCs.
The group says that ASHM is much less common than ASM, and that different mechanisms probably control these mods. They also note that these results may help others interpret genome-wide association studies (GWAS) and provide more insight into the etiology of developmental disorders.
Spot the differences at Epigenetics & Chromatin, May 2012.