|
| Status |
Public on Nov 10, 2020 |
| Title |
Chromatin topology and the timing of enhancer function at the HoxD locus [4C-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
In tetrapods, the HoxD gene cluster is critical for proper limb formation. In the emerging limb buds, different sub-groups of Hoxd genes respond first to a proximal regulatory signal, then to a distal signal that organizes digits. These two regulations emanate from the two TADs flanking HoxD, both containing a range of appropriate enhancer sequences. The telomeric TAD (T-DOM) contains several regulatory elements controlling Hoxd genes, initially in a temporal manner and then in the proximal presumptive forearm. T-DOM is divided into two sub-TADs separated by a CTCF-rich boundary defining two regulatory modules with most limb enhancers concentrated in the more distant module. In order to understand the importance of this regulatory topology to elicit a precise Hoxd gene transcription in time and space, we both deleted or inverted this sub-TAD boundary and eliminated the CTCF binding sites. These perturbations caused a time delay in gene activation, which was subsequently resumed. We then inverted the entire T-DOM to change the respective position of the two sub-TADs, which concomitantly introduced a TAD boundary between HoxD and the inverted T-DOM. This re-arrangement had a stronger impact on the early expression and flattened the Hoxd mRNAs levels. The latter effect was rescued by re-granting access to the enhancers upon deletion of the ectopic boundary. These results highlight the importance of regulatory topologies in the temporal control of gene expression. We also show that, along with time, the affinity of enhancers to find their natural target genes can overcome the presence of both a strong TAD border, and an unfavourable orientation of CTCF sites.
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| |
|
| Overall design |
4C-seq analysis of several viewpoints inside ther HoxD gene cluster and on the telomeric gene desert in developing mouse limb tissues.
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| |
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| Contributor(s) |
Rodríguez-Carballo E, Lopez-Delisle L, Duboule D |
| Citation(s) |
33229569 |
| |
| Submission date |
Jul 10, 2020 |
| Last update date |
Jan 04, 2021 |
| Contact name |
Eddie Rodríguez-Carballo |
| E-mail(s) |
edgardo.rodriguez@unige.ch
|
| Organization name |
Université de Genève
|
| Department |
Department of Genetics and Evolution
|
| Street address |
4, Boulevard d'Yvoy
|
| City |
Geneva |
| ZIP/Postal code |
1205 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (59)
|
|
| This SubSeries is part of SuperSeries: |
| GSE154189 |
Chromatin topology and the timing of enhancer function at the HoxD locus |
|
| Relations |
| BioProject |
PRJNA645388 |
| SRA |
SRP271258 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE154186_RAW.tar |
142.3 Mb |
(http)(custom) |
TAR (of BEDGRAPH, BW) |
| GSE154186_allVhic.tar.gz |
19.2 Mb |
(ftp)(http) |
TAR |
| GSE154186_average__E12_PFL_delCTCFs__all.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_delCTCFs__cluster1.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_delCTCFs__cluster2.cool.gz |
14.8 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_invTDOM__all.cool.gz |
14.9 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_invTDOMdelBd__all.cool.gz |
14.9 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_invTDOMdelBd__cluster1.cool.gz |
15.0 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_invTDOMdelBd__cluster2.cool.gz |
14.9 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_invTDOMdelBd__cluster3.cool.gz |
15.0 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_wt__all.cool.gz |
14.3 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_wt__cluster1.cool.gz |
14.4 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E12_PFL_wt__cluster2.cool.gz |
14.5 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_delCS3840__all.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_delCS3840__cluster1.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_delCS3840__cluster2.cool.gz |
14.4 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_delCS3840__cluster3.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invCS3840__all.cool.gz |
14.5 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invCS3840__cluster1.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invCS3840__cluster2.cool.gz |
14.5 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invCS3840__cluster3.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invCS3840__cluster4.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invTDOM__all.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invTDOM__cluster1.cool.gz |
14.8 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_invTDOM__cluster2.cool.gz |
15.0 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_delCS3840__all.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_delCS3840__cluster1.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_delCS3840__cluster2.cool.gz |
14.8 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_invCS3840__all.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_invTDOM__all.cool.gz |
14.6 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_invTDOM__cluster1.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
| GSE154186_average__E9_FLB_wt_like_invTDOM__cluster2.cool.gz |
14.7 Kb |
(ftp)(http) |
COOL |
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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