|
| Status |
Public on Jul 18, 2024 |
| Title |
CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Third-party reanalysis
|
| Summary |
In mammals, tail length is controlled by several genetic determinants, amongst which Hox13 genes located at the posterior extremities of Hox clusters, whose main function are to terminate the extension of the body axis. In this view, the precise timing in the transcriptional activation of these genes may impact upon body length. Unlike other Hox clusters, HoxB lacks all posterior genes between Hoxb9 and Hoxb13, two genes separated by a ca. 70 kb large DNA segment containing an unusually high number of CTCF sites, suggesting it isolates Hoxb13 from the rest of the cluster, thereby delaying its negative impact on trunk extension. We deleted the spacer DNA to induce a potential heterochronic gain of function of Hoxb13 at physiological concentration and observed a shortening of the tail as well as other abnormal phenotypes, which were all rescued by inactivating Hoxb13 in-cis with the deletion. A comparable gain of function was observed in mutant ES cells grown as pseudo-embryos in vitro, which allowed us to examine in details the importance of both the number and the orientation of CTCF sites in the insulating activity of the DNA spacer. A short cassette containing all the CTCF sites was sufficient to insulate Hoxb13 from the rest of HoxB and additional modifications of this CTCF cassette showed that two CTCF sites in convergent orientations are already capable of importantly delaying Hoxb13 activation in these conditions. We discuss the relative importance of genomic distance versus number and orientation of CTCF sites in preventing Hoxb13 to be activated too early during trunk extension and hence to modulate tail length.
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| |
|
| Overall design |
scRNA-seq of HoxB mutated 144h gastruloid
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The table below lists GEO accessions reused/reanalyzed for this study.
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| Contributor(s) |
Bochaton C, Mayran A, Lopez-Delisle L, Zakany J, Rekaik H, Duboule D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jul 17, 2024 |
| Last update date |
Jul 19, 2024 |
| Contact name |
Lucille Lopez-Delisle |
| E-mail(s) |
lucille.delisle@epfl.ch
|
| Organization name |
EPFL
|
| Street address |
Station 19
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (1) |
| GSM8403290 |
scRNA-seq of HoxB Del(i9-13)/+ 144h gastruloid |
|
| This SubSeries is part of SuperSeries: |
| GSE272483 |
CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length |
|
| Relations |
| Reanalysis of |
GSM7890942 |
| BioProject |
PRJNA1136947 |
