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| Status |
Public on Jan 22, 2015 |
| Title |
Analysis of allele specific expression and its chromatin state to identify genes that are escaping X chromosome inactivation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Disappearance of the Barr body has long been considered a hallmark of cancer, although whether this corresponds to epigenetic instability and transcriptional reactivation, or to genetic loss, has remained unclear. Here we show that in breast cancer cell lines as well as primary breast tumors, the inactive X chromosome frequently displays a highly abnormal 3D nuclear organization, with global perturbations in its characteristic heterochromatic state, including apparent gain of euchromatic marks and lessening of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells accompanied by a significant degree of X-linked gene reactivation, affecting genes previously implicated in cancer, including the histone deacetylase, HDAC8 and transducin (Beta)-Like 1X-Linked, TBL1X. We provide proof of principle that epigenetic deregulation can indeed perturb the dosage of some X-linked factors and demonstrate that many of these genes are reactivated in primary breast tumors. Our study establishes that the inactive X is subject to epigenetic erosion in a cancer context and sets the stage for the use of chromatin marks and X- chromosome genes as potential biomarkers to assess epigenetic changes in cancer.
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| Overall design |
Examination of allele specific expression of genes in chrX using histone marks, transcriptome, exome and SNP data on two normal cell-line and three cancer cell-line.
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| Contributor(s) |
Chaligne R, Popova T, Mendoza-Parra M, Saleem MM, Gentien D, Ban K, Piolot T, Leroy O, Mariani O, Gronemeyer H, Vincent-Salomon A, Stern M, Heard E |
| Citation(s) |
25653311 |
| Submission date |
Nov 04, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ronan Chaligné |
| E-mail(s) |
Ronan.Chaligne@curie.fr
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| Organization name |
Institut Curie
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| Lab |
Edith Heard's lab
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| Street address |
26, Rue d'Ulm
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| City |
Paris |
| ZIP/Postal code |
75248 |
| Country |
France |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (29)
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| This SubSeries is part of SuperSeries: |
| GSE62907 |
The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer |
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| Relations |
| BioProject |
PRJNA266312 |
| SRA |
SRP049507 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE62966_HMEC-table-simple_1KbFlankingRegion_Absolute.xls.gz |
98.3 Kb |
(ftp)(http) |
XLS |
| GSE62966_HMEC_ChIP-Exome-mRNA_combined.snps.txt.gz |
3.6 Kb |
(ftp)(http) |
TXT |
| GSE62966_MDAMB436-table-simple_1KbFlankingRegion_Absolute.xls.gz |
114.0 Kb |
(ftp)(http) |
XLS |
| GSE62966_MDAMB436_ChIP-Exome-mRNA_combined.snps.txt.gz |
213.4 Kb |
(ftp)(http) |
TXT |
| GSE62966_RAW.tar |
391.5 Mb |
(http)(custom) |
TAR (of BEDGRAPH, FPKM_TRACKING) |
| GSE62966_SKBR3-table-simple_1KbFlankingRegion_Absolute.xls.gz |
105.2 Kb |
(ftp)(http) |
XLS |
| GSE62966_SKBR3_ChIP-Exome-mRNA_combined.snps.txt.gz |
205.7 Kb |
(ftp)(http) |
TXT |
| GSE62966_WI38-table-simple_1KbFlankingRegion_Absolute.xls.gz |
110.2 Kb |
(ftp)(http) |
XLS |
| GSE62966_WI38_ChIP-Exome-mRNA_combined.snps.txt.gz |
211.3 Kb |
(ftp)(http) |
TXT |
| GSE62966_ZR751-table-simple_1KbFlankingRegion_Absolute.xls.gz |
100.5 Kb |
(ftp)(http) |
XLS |
| GSE62966_ZR751_ChIP-Exome-mRNA_combined.snps.txt.gz |
202.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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