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Series GSE60275 Query DataSets for GSE60275
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
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.
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.
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
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
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (927)
GSM1469046 F_PM_A026L
GSM1469047 F_PM_A031D
GSM1469048 F_PM_A035F
BioProject PRJNA257897

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60275_RAW.tar 183.1 Mb (http)(custom) TAR
GSE60275_signalA_signalB.txt.gz 47.3 Mb (ftp)(http) TXT
Processed data included within Sample table

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