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| Status |
Public on Oct 05, 2020 |
| Title |
Specific ectodermal enhancers control the expression of Hoxc genes in developing mammalian teguments [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Vertebrate Hox genes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function of Hoxc13, which is causative of the ectodermal dysplasia 9 (ECTD9) syndrome in human patients. We further identified, in mammals only, two ectodermal-specific enhancers located upstream the gene cluster, which act synergistically to regulate Hoxc genes in these ectodermal organs. Deletion of these enhancers alone or in combination revealed a strong quantitative component in the regulation of these genes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.
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| |
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| Overall design |
ATAC-seq datasets of ectoderm of the distal part of forelimb and hindlimb at E14.5 as well as E13.5 forebrain
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| Contributor(s) |
Fernandez-Guerrero M, Bolt CC, Lopez-Delisle L, Duboule D, Ros M |
| Citation(s) |
33199643 |
| |
| Submission date |
May 15, 2020 |
| Last update date |
Jan 25, 2021 |
| Contact name |
Lucille Lopez-Delisle |
| E-mail(s) |
lucille.delisle@epfl.ch
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| Organization name |
EPFL
|
| Street address |
Station 19
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE150702 |
Specific ectodermal enhancers control the expression of Hoxc genes in developing mammalian teguments |
|
| Relations |
| BioProject |
PRJNA633173 |
| SRA |
SRP261908 |
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