caa a22 4500 445861150 CHVBK 20180317145443.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00439-011-1007-8 doi (NATIONALLICENCE)springer-10.1007/s00439-011-1007-8 Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation [Elektronische Daten] [Allison Cotton, Lucia Lam, Joslynn Affleck, Ian Wilson, Maria Peñaherrera, Deborah McFadden, Michael Kobor, Wan Lam, Wendy Robinson, Carolyn Brown] X-chromosome inactivation (XCI) results in the differential marking of the active and inactive X with epigenetic modifications including DNA methylation. Consistent with the previous studies showing that CpG island-containing promoters of genes subject to XCI are approximately 50% methylated in females and unmethylated in males while genes which escape XCI are unmethylated in both sexes; our chromosome-wide (Methylated DNA ImmunoPrecipitation) and promoter-targeted methylation analyses (Illumina Infinium HumanMethylation27 array) showed the largest methylation difference (D=0.12, p<2.2 E−16) between male and female blood at X-linked CpG islands promoters. We used the methylation differences between males and females to predict XCI statuses in blood and found that 81% had the same XCI status as previously determined using expression data. Most genes (83%) showed the same XCI status across tissues (blood, fetal: muscle, kidney and nerual); however, the methylation of a subset of genes predicted different XCI statuses in different tissues. Using previously published expression data the effect of transcription on gene-body methylation was investigated and while X-linked introns of highly expressed genes were more methylated than the introns of lowly expressed genes, exonic methylation did not differ based on expression level. We conclude that the XCI status predicted using methylation of X-linked promoters with CpG islands was usually the same as determined by expression analysis and that 12% of X-linked genes examined show tissue-specific XCI whereby a gene has a different XCI status in at least one of the four tissues examined. The Author(s), 2011 Cotton Allison Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Lam Lucia Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Affleck Joslynn Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Wilson Ian British Columbia Cancer Research Centre, Vancouver, BC, Canada aut Peñaherrera Maria Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut McFadden Deborah Child and Family Research Institute, Vancouver, BC, Canada aut Kobor Michael Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Lam Wan British Columbia Cancer Research Centre, Vancouver, BC, Canada aut Robinson Wendy Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Brown Carolyn Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut Human Genetics Springer-Verlag 130/2(2011-08-01), 187-201 0340-6717 130:2<187 2011 130 439 https://doi.org/10.1007/s00439-011-1007-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-1007-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cotton Allison Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Lam Lucia Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Affleck Joslynn Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Wilson Ian British Columbia Cancer Research Centre, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Peñaherrera Maria Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- McFadden Deborah Child and Family Research Institute, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Kobor Michael Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Lam Wan British Columbia Cancer Research Centre, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Robinson Wendy Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Brown Carolyn Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/2(2011-08-01), 187-201 0340-6717 130:2<187 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer