| Autor: |
Duncan CG; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Grimm SA; Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Morgan DL; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Bushel PR; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Bennett BD; Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Roberts JD; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Tyson FL; Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Merrick BA; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Wade PA; Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. wadep2@niehs.nih.gov. |
| Abstrakt: |
DNA methylation plays a key role in X-chromosome inactivation (XCI), a process that achieves dosage compensation for X-encoded gene products between mammalian female and male cells. However, differential sex chromosome dosage complicates genome-wide epigenomic assessments, and the X chromosome is frequently excluded from female-to-male comparative analyses. Using the X chromosome in the sexually dimorphic mouse liver as a model, we provide a general framework for comparing base-resolution DNA methylation patterns across samples that have different chromosome numbers and ask at a systematic level if predictions by historical analyses of X-linked DNA methylation hold true at a base-resolution chromosome-wide level. We demonstrate that sex-specific methylation patterns on the X chromosome largely reflect the effects of XCI. While our observations concur with longstanding observations of XCI at promoter-proximal CpG islands, we provide evidence that sex-specific DNA methylation differences are not limited to CpG island boundaries. Moreover, these data support a model in which maintenance of CpG islands in the inactive state does not require complete regional methylation. Further, we validate an intragenic non-CpG methylation signature in genes escaping XCI in mouse liver. Our analyses provide insight into underlying methylation patterns that should be considered when assessing sex differences in genome-wide methylation analyses. |
