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Status |
Public on Jul 18, 2024 |
Title |
CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length [RNA-seq embryo] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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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 |
RNA-seq of HoxB mutated and wild-type littermates headless embryos at E9.5 and E10.5
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Contributor(s) |
Zakany J, Lopez-Delisle L, Bochaton C, Rekaik H, Duboule D |
Citation missing |
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Submission date |
Jul 16, 2024 |
Last update date |
Jul 19, 2024 |
Contact name |
Lucille Lopez-Delisle |
E-mail(s) |
lucille.delisle@epfl.ch
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Organization name |
EPFL
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Street address |
Station 19
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City |
Lausanne |
ZIP/Postal code |
1015 |
Country |
Switzerland |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (18)
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GSM8399771 |
RNA-seq of E9.5 headless embryo wild-type replicate 1 |
GSM8399772 |
RNA-seq of E9.5 headless embryo wild-type replicate 2 |
GSM8399773 |
RNA-seq of E9.5 headless embryo wild-type replicate 3 |
GSM8399774 |
RNA-seq of E9.5 headless embryo HoxB Del(i9-13) homozygous replicate 1 |
GSM8399775 |
RNA-seq of E9.5 headless embryo HoxB Del(i9-13) homozygous replicate 2 |
GSM8399776 |
RNA-seq of E9.5 headless embryo HoxB Del(i9-13) homozygous replicate 3 |
GSM8399777 |
RNA-seq of E10.5 headless embryo wild-type replicate 1 |
GSM8399778 |
RNA-seq of E10.5 headless embryo wild-type replicate 2 |
GSM8399779 |
RNA-seq of E10.5 headless embryo wild-type replicate 3 |
GSM8399780 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13) homozygous replicate 1 |
GSM8399781 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13) homozygous replicate 2 |
GSM8399782 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13) homozygous replicate 3 |
GSM8399783 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13):Hoxb13hd homozygous replicate 1 |
GSM8399784 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13):Hoxb13hd homozygous replicate 2 |
GSM8399785 |
RNA-seq of E10.5 headless embryo HoxB Del(i9-13):Hoxb13hd homozygous replicate 3 |
GSM8399786 |
RNA-seq of E10.5 headless embryo Hoxb13hd homozygous replicate 1 |
GSM8399787 |
RNA-seq of E10.5 headless embryo Hoxb13hd homozygous replicate 2 |
GSM8399788 |
RNA-seq of E10.5 headless embryo Hoxb13hd homozygous replicate 3 |
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This SubSeries is part of SuperSeries: |
GSE272483 |
CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length |
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Relations |
BioProject |
PRJNA1136541 |