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Status |
Public on Dec 01, 2014 |
Title |
Differential spatial and structural organization of the X chromosome underlies dosage compensation in C. elegans. |
Organism |
Caenorhabditis elegans |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The essential adaptation of X-linked gene expression to the X chromosome copy number variation (called dosage compensation, DC) has been widely studied as a model of chromosome-wide gene regulation. In C. elegans, DC is achieved by two fold downregulation of gene expression from both X copies in hermaphrodites. The dosage compensation complex (DCC), a multiprotein complex structurally similar to mitotic condensins, restricts RNA polymerase progression. Higher order chromatin structures have therefore long been suggested to regulate X-linked gene expression. Here we show that in C. elegans males, the single X chromosome interacts broadly with nuclear pores, while in hermaphrodites the DCC impairs this interaction. Using microscopic measurements we find that the X chromosome is located at the nuclear periphery in males and internal in hermaphrodites, while compaction was higher for the X chromosome than for autosomes but surprisingly comparable between sexes. Mechanistically, we show that a single motif enriched on X, sufficient for DCC loading in hermaphrodites, autonomously targets an autosomal locus to the nuclear periphery specifically in males. Using DNA adenine methyltransferase identification (DamID), we demonstrate that the perinuclear interaction domains are nuclear pores. Dynamic polymer modeling shows that this discrete pore anchoring can explain the high compaction of the male X chromosome. Together, our results put forward a structural model of DC, by demonstrating that X-specific sequences mediate interactions with nuclear pores, thereby locating the X chromosome in active perinuclear domains, while the DCC physically moves X-linked genes away from these transcriptionally active neighborhoods.
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Overall design |
Examination of DamID pattern in 3 different strains with at least 2 replicates per strain, in male or hermaphrodite L4 animals
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Contributor(s) |
Sharma R, Jost D, Kind J, Gómez-Saldivar G, van Steensel B, Askjaer P, Vaillant C, Meister P |
Citation(s) |
25452271 |
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Submission date |
Mar 27, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Peter Meister |
E-mail(s) |
peter.meister@unibe.ch
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Phone |
+41316844609
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Organization name |
University of Bern
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Department |
Institute of Cell Biology
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Lab |
Cell Fate and Nuclear Organization
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Street address |
Baltzerstrasse 4
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City |
Bern |
State/province |
Schweiz |
ZIP/Postal code |
3012 |
Country |
Switzerland |
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Platforms (1) |
GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
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Samples (6)
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Relations |
BioProject |
PRJNA242811 |
SRA |
SRP040625 |
Supplementary file |
Size |
Download |
File type/resource |
GSE56270_GATC_read_counts_per_100kb_bin.tab.gz |
16.8 Kb |
(ftp)(http) |
TAB |
GSE56270_Ratios_per_100kb_bin.tab.gz |
26.0 Kb |
(ftp)(http) |
TAB |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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