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| Status |
Public on Jun 01, 2015 |
| Title |
HSA21 Single-minded 2 (Sim2) binding sites co-localize with super-enhancers and pioneer transcription factors in pluripotent mouse ES cells [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Down syndrome (DS) results from trisomy of chromosome 21 (HSA21). Some DS phenotypes may be directly or indirectly related to the increased expression of specific HSA21 genes, in particular those encoding transcription factors. The HSA21 encoded Single-minded 2 (SIM2) transcription factor has key neurological functions and is a good candidate to be involved in the cognitive impairment of DS. ChIP-sequencing was used to map SIM2 binding in mouse embryonic stem cells and has revealed 1229 high-confidence SIM2-binding sites. Analysis of the SIM2 target genes confirmed the importance of SIM2 in developmental and neuronal processes and indicated that SIM2 may be a master transcription regulator. Indeed, SIM2 DNA binding sites share sequence specificity and overlapping domains of occupancy with master transcription factors such as SOX2, OCT4, NANOG or KLF4. The association between SIM2 and these pioneer factors is supported by the finding that SIM2 can be co-immunoprecipitated with SOX2, OCT4, NANOG or KLF4. Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). Altogether, we provide evidence that SIM2 binds a specific set of enhancer elements thus explaining how SIM2 can regulate its gene network in DS neuronal features.
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| Overall design |
ChIP-Seq analysis of transcription factor binding sites in mES cells: Sim2 (in 3 replicates named A6, B8, C4 and in a control line named EB3), Oct4, Sox2, Nanog, Med1 and Med12 (in the A6 line).
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| Contributor(s) |
Letourneau A, Cobellis G, Fort A, Santoni FA, Garieri M, Falconnet E, Ribaux P, Vannier A, Guipponi M, Carninci P, Borel C, Antonarakis SE |
| Citation(s) |
25955728 |
| |
| Submission date |
Jul 14, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Audrey Letourneau |
| E-mail(s) |
audrey.letourneau@unige.ch
|
| Organization name |
University of Geneva Medical School
|
| Department |
Genetic Medicine and Development
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| Street address |
Rue Michel-Servet 1
|
| City |
Geneva |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE59379 |
HSA21 Single-minded 2 (Sim2) binding sites co-localize with super-enhancers and pioneer transcription factors in pluripotent mouse ES cells. |
|
| Relations |
| BioProject |
PRJNA255218 |
| SRA |
SRP044302 |
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