 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 03, 2015 |
| Title |
Condensin-Driven Remodeling of X-Chromosome Topology during Dosage Compensation [Hi-C] |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Other
|
| Summary |
The three-dimensional (3D) organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure or how structure influences gene expression. Here we exploit the X-chromosome-wide process of dosage compensation to dissect these mechanisms. The dosage compensation complex (DCC) of C. elegans, a condensin complex, binds to both X chromosomes of hermaphrodites via sequence-specific recruitment sites (rex sites) to reduce chromosome-wide gene expression by half. Using genome-wide chromosome conformation capture and single-cell FISH to compare chromosome structure in wild-type and DCC-defective embryos (DC mutants), we show that the DCC remodels X chromosomes of hermaphrodites into a spatial conformation distinct from autosomes. The dosage-compensated X chromosomes are composed of Topologically Associating Domains (TADs) that have sharper boundaries and more regular spacing than TADs on autosomes. Most TAD boundaries on X coincide with the highest-affinity rex sites, and these boundaries are lost or diminished in DC mutants, thereby restoring the topology of X to a native conformation resembling that of autosomes. Although most rex sites engage in multiple strong DCC-dependent long-range interactions, the strongest interactions occur between rex sites at the DCC-dependent TAD boundaries. We propose the DCC actively shapes the topology of the entire X chromosome by forming new TAD boundaries and reinforcing pre-existing weak TAD boundaries through interactions between its highest affinity sites. Such changes in higher-order X-chromosome structure then influence gene expression over long distances.
|
| |
|
| Overall design |
Our goal was to determine the molecular topology of the dosage compensated X chromosomes of C. elegans. To do so we performed Hi-C analysis and FISH analysis in wild-type XX embryos and mutant XX embryos in which the dosage compensation complex was defective and could therefore not bind to the X chromosome. We showed the dosage compensation complex actively shapes the topology of the entire X chromosome and creates a unique, sex-specific Xconformation that differs from the conformation of autosomes. RNA-seq experiments in wild-type and mutant embryos permitted a comparison between changes in chromosome structure and changes in gene expression.
|
| |
|
| Contributor(s) |
Crane E, Bian Q, McCord RP, Lajoie BR, Wheeler BS, Ralston EJ, Uzawa S, Dekker J, Meyer BJ |
| Citation(s) |
26030525 |
| |
| Submission date |
Nov 28, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Barbara J. Meyer |
| E-mail(s) |
bjmeyer@berkeley.edu
|
| Phone |
510 643 5583
|
| Organization name |
HHMI/UCB
|
| Department |
MCB
|
| Lab |
Meyer
|
| Street address |
16 Barker Hall #3204
|
| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
|
| Samples (2) |
|
| This SubSeries is part of SuperSeries: |
| GSE59716 |
Condensin-Driven Remodeling of X-Chromosome Topology during Dosage Compensation |
|
| Relations |
| BioProject |
PRJNA268850 |
| SRA |
SRP050343 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63717_HiC_libraries_Info.xls.gz |
9.2 Kb |
(ftp)(http) |
XLS |
| GSE63717_RAW.tar |
89.6 Mb |
(http)(custom) |
TAR (of TAR) |
| GSE63717_SRy93-N2-DpnII-zScoreDifference.tar.gz |
21.9 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
