A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci 



1756-8935-5-6-s1.xls: Number of mapped reads for each dataset used in this study. 1756-8935-5-6-s1.xls: Read counts for each allele and each histone modification at the sites of ASHM identified in this study. 1756-8935-5-6-s1.xls: Sites of ASHM and their distance to corresponding annotations. 1756-8935-5-6-s4.pdf: Location of ASE and ASHM sites at the 17q12 locus. 1756-8935-5-6-s5.xls: H1 Bisulfite sequencing dataset comparison. 1756-8935-5-6-s6.xls: Datasets used in this analysis. 1756-8935-5-6-s5.pdf: Description of method for calling sites of ASHM. 1756-8935-5-6-s5.pdf: ASHM site quality control (A) Coverage of Bisulfite sequencing reads across the whole genome and at sites of ASHM only. 0.26% of sites in the whole genome analysis had coverages of greater than 100, but these have been excluded from this plot. The mean coverage at sites of ASHM was 23x as opposed to the genome-wide mean coverage of 32 x. (B) Hardy-Weinberg equilibrium (HWE) P-values at 54 ASHM site polymorphisms (i.e. before HWE filtering) and at all high-coverage sites.



Chromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites 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 in human embryonic stem cells (hESCs).


Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.


These results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.

Data Citation

Prendergast, James; Tong, Pin; Hay, David; Farrington, Susan; Semple, Colin. (2012). A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci, [dataset]. http://dx.doi.org/10.7488/ds/147.
Date made available31 Oct 2012
PublisherEdinburgh DataShare

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