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Status |
Public on Jul 18, 2016 |
Title |
Structural organization of the inactive X chromosome |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other Third-party reanalysis
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Summary |
X-chromosome inactivation (XCI) entails a massive structural reorganization of the inactive X (Xi). However the molecular architecture of the Xi is unknown. Here we show that the Xi lacks typical autosomal features such as active/inactive compartments and topologically associating domains (TADs), except around a small number of genes that escape XCI and remain expressed. Escaping genes form TADs and retain DNA accessibility at promoter-proximal and CTCF binding sites, indicating that these loci can avoid Xist-mediated erasure of chromosomal structure. We further show that genesilencing competent Xist RNA is sufficient to induce segregation of the Xi into two ‘mega-domains’ separated by a boundary that includes the DXZ4 macrosatellite. Deletion of this boundary prior to XCI results in fusion of the megadomains and altered patterns of escape that correlate with changes in TAD structure following differentiation and XCI . Our results suggest a critical role for the boundary locus and Xist RNA in shaping the structure of the Xi and modulating escape from XCI. Our findings also point to roles of transcription and CTCF binding in TAD formation in the context of facultative heterochromatin.
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Overall design |
Allele specific Hi-C, Allele specific ATAC-seq and Allele specific RNA-seq. Mouse 129/cast female.
Processed data for two reanalyzed RNA-seq Samples, GSM1305895 and GSM1305900, are included in this study and are linked to the Series record, GSE72697_rpkm_bedGraph_ESC.tar.gz and GSE72697_rpkm_bedGraph_NPC-deltaFT.tar.gz.
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Contributor(s) |
Giorgetti L, Lajoie BR, Carter AC, Attia M, Zhan Y, Xu J, Chen C, Kaplan N, Chang HY, Heard E, Dekker J |
Citation(s) |
27437574 |
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Submission date |
Sep 03, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Bryan R Lajoie |
E-mail(s) |
bryan.lajoie@gmail.com
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Organization name |
UMMS
|
Department |
Program in Systems Biology
|
Lab |
Dekker Lab
|
Street address |
368 Plantation St.
|
City |
Worcester |
State/province |
MA |
ZIP/Postal code |
01605 |
Country |
USA |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (8)
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Relations |
Reanalysis of |
GSM1305895 |
Reanalysis of |
GSM1305900 |
BioProject |
PRJNA294714 |
SRA |
SRP063320 |
Supplementary file |
Size |
Download |
File type/resource |
GSE72697_HIC_readme.txt |
2.6 Kb |
(ftp)(http) |
TXT |
GSE72697_RAW.tar |
25.3 Gb |
(http)(custom) |
TAR (of TAR) |
GSE72697_RNA-seq_readme.txt |
904 b |
(ftp)(http) |
TXT |
GSE72697_annotation-tracks.tar.gz |
48.2 Kb |
(ftp)(http) |
TAR |
GSE72697_annotation_tracks.readme.txt |
947 b |
(ftp)(http) |
TXT |
GSE72697_expressed_bed_ESC.tar.gz |
563.6 Kb |
(ftp)(http) |
TAR |
GSE72697_expressed_bed_NPC-deltaFT.tar.gz |
572.7 Kb |
(ftp)(http) |
TAR |
GSE72697_insulation-difference.tar.gz |
1.7 Mb |
(ftp)(http) |
TAR |
GSE72697_merged.tar.gz |
7.1 Mb |
(ftp)(http) |
TAR |
GSE72697_readme.txt.gz |
662 b |
(ftp)(http) |
TXT |
GSE72697_rpkm_bedGraph_ESC.tar.gz |
620.4 Kb |
(ftp)(http) |
TAR |
GSE72697_rpkm_bedGraph_NPC-deltaFT.tar.gz |
570.5 Kb |
(ftp)(http) |
TAR |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |