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

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Title: A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci
Data Creator: Prendergast, James; Tong, Pin; Hay, David; Farrington, Susan; Semple, Colin
Date Available: 2012-10-31
Citation: Prendergast, James; Tong, Pin; Hay, David; Farrington, Susan; Semple, Colin. (2014). 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.
Dataset Description (abstract): Background 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). Results 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. Conclusion 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.

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Files Size Format View Description
A genome-wide screen_readme.docx 14.74Kb Microsoft Word 2007 Download Introduction text
1756-8935-5-6-s1.xlsx 11.28Kb Microsoft Excel 2007 Download Number of mapped reads for each dataset
1756-8935-5-6-s2.xlsx 119.3Kb Microsoft Excel 2007 Download Read counts for each allele and each histone modification at the sites of ASHM identified in this study.
1756-8935-5-6-s3.xlsx 14.78Kb Microsoft Excel 2007 Download Sites of ASHM and their distance to corresponding annotations.
1756-8935-5-6-s4.pdf 3.134Mb PDF Download Location of ASE and ASHM sites at the 17q12 locus.
1756-8935-5-6-s5.xlsx 13.73Kb Microsoft Excel 2007 Download H1 Bisulfite sequencing dataset comparison
1756-8935-5-6-s6.xlsx 19.19Kb Microsoft Excel 2007 Download Datasets used in this analysis.
1756-8935-5-6-s7.pdf 296.9Kb PDF Download Description of method for calling sites of ASHM.
1756-8935-5-6-s8.pdf 981.7Kb PDF Download ASHM site quality control
1756-8935-5-6-s1.csv 1.207Kb Text file Download Number of mapped reads for each dataset
1756-8935-5-6-s2_H1.csv 180.2Kb Text file Download Read counts for each allele and each histone modification at the sites of ASHM identified in this study (H1 cell line).
1756-8935-5-6-s2_IMR90.csv 8.027Kb Text file Download Read counts for each allele and each histone modification at the sites of ASHM identified in this study (IMR90 cell line).
1756-8935-5-6-s3.csv 5.009Kb Text file Download Sites of ASHM and their distance to corresponding annotations.
1756-8935-5-6-s5.csv 3.940Kb Text file Download H1 Bisulfite sequencing dataset comparison
1756-8935-5-6-s6_H1.csv 14.40Kb Text file Download Datasets used in this analysis (H1 cell line).
1756-8935-5-6-s6_IMR90.csv 7.352Kb Text file Download Datasets used in this analysis (IMR90 cell line).

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