Human Embryonic Stem Cells Reveals Novel Sites of Alele-Specific Histone Modification
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Chromatin structure at a given site can differ between chromosome copies in a cell, and suchimbalances in chromatin structure have been shown to be important in understanding themolecular mechanisms controlling several disease loci. Human genetic variation, DNAmethylation, and disease have been intensely studied, uncovering many sites of allele-specificDNA methylation (ASM).
However, little is known about the genome-wide occurrence ofsites of allele-specific histone modification (ASHM) and their relationship to human disease.The aim of this study was to investigate the extent and characteristics of sites of ASHM inhuman embryonic stem cells (hESCs).
Results: Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM inhESCs, and their relationship to sites of allele-specific expression (ASE) and DNAmethylation. We found that, although they were rare, sites of ASHM were substantiallyenriched at loci displaying ASE.
Many were also found at known imprinted regions, hencesites of ASHM are likely to be better markers of imprinted regions than sites of ASM. Wealso found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmentalsyndromes mediated by deletions, providing insights into the etiology of these disorders.
Conclusion: These results demonstrate the potential importance of ASHM patterns in the interpretation ofdisease loci, and the protocol described provides a basis for similar studies of ASHM in othercell types to further our understanding of human disease susceptibility.
Author: James GD PrendergastPin TongDavid C HaySusan M FarringtonColin AM Semple
Credits/Source: Epigenetics &Chromatin 2012, 5:6