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| Status |
Public on Nov 29, 2014 |
| Title |
Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation. |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
X-chromosome inactivation (XCI) achieves dosage compensation between males and females through the silencing of the majority of genes on one X chromosome, with approximately 15% of genes reported to show inactive X (Xi) expression. We examined the interplay between ChromHMM states, CpG density, expression and DNAm from over 1800 female samples with the Illumina 450K array. The interaction between CpG density and histone marks differed between the active X (Xa) and the Xi, with X-linked promoters reflecting transcriptional status, while the Xi showed lower DNAm than the Xa at all non-promoter regions. Promoter DNAm was used to determine a novel XCI status for more than 100 transcription start sites and a comparison across 27 tissues revealed the majority of genes were consistently subject to XCI. Inter-female and twin data supported a model of predominately cis-acting influences on escape, or variable escape, from XCI. Increased promoter DNAm at escape genes correlated with decreased relative Xi expression up to ~15% female DNAm but above this threshold DNAm was not correlated with the stability of silencing. Xi DNAm was ~12% lower than Xa DNAm within the gene bodies of subject genes and between genes while there was equivalent DNAm at escape genes. In addition to offering insight into sex-specific difference in disease, female X chromosomes provide the opportunity to compare euchromatin and heterochromatin of allelic regions within the same nuclear environment and demonstrate the correlation of DNAm with transcription and the influences of CpG density and chromatin marks.
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| Overall design |
This cohort consist of genomic DNA extracted from 927 indiviudals representing 5 tissues, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling from only the X chromosome.
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| Contributor(s) |
Cotton AM, Price EM, Jones MJ, Kobor MS, Brown CJ |
| Citation(s) |
25381334 |
| Submission date |
Aug 08, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Carolyn J Brown |
| E-mail(s) |
cbrown@ubc.ca
|
| Organization name |
University of British Columbia
|
| Department |
Medical Genetics
|
| Lab |
Brown Lab
|
| Street address |
2350 Health Sciences Mall
|
| City |
Vancouver |
| State/province |
British Columbia |
| ZIP/Postal code |
V6T1Z3 |
| Country |
Canada |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (927)
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| Relations |
| BioProject |
PRJNA257897 |
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