A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-05-01
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| Series: | Epigenetics & Chromatin |
| Online Access: | http://www.epigeneticsandchromatin.com/content/5/1/6 |
| _version_ | 1819036554337714176 |
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| author | Prendergast James G D Tong Pin Hay David C Farrington Susan M Semple Colin A M |
| author_facet | Prendergast James G D Tong Pin Hay David C Farrington Susan M Semple Colin A M |
| author_sort | Prendergast James G D |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-21T08:07:22Z |
| format | Article |
| id | doaj.art-fa2435048cfa4faf93ee75dfbda7500f |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-21T08:07:22Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-fa2435048cfa4faf93ee75dfbda7500f2022-12-21T19:10:46ZengBMCEpigenetics & Chromatin1756-89352012-05-0151610.1186/1756-8935-5-6A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease lociPrendergast James G DTong PinHay David CFarrington Susan MSemple Colin A M<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>http://www.epigeneticsandchromatin.com/content/5/1/6 |
| spellingShingle | Prendergast James G D Tong Pin Hay David C Farrington Susan M Semple Colin A M A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci Epigenetics & Chromatin |
| title | A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci |
| title_full | A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci |
| title_fullStr | A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci |
| title_full_unstemmed | A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci |
| title_short | A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci |
| title_sort | genome wide screen in human embryonic stem cells reveals novel sites of allele specific histone modification associated with known disease loci |
| url | http://www.epigeneticsandchromatin.com/content/5/1/6 |
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