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| Status |
Public on Jun 12, 2012 |
| Title |
ChIP-sequencing (ChIP-seq) experiments on female ESCs expressing V5-tagged REX1 and control wild-type Embryonic stem cells (ESCs) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome (XCI) in all female somatic cells. Up-regulation of Xist transcription on the future inactive X chromosome (Xi) acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to XCI. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is up-regulated in differentiating mouse embryonic stem cells (ESCs) and activates Xist transcription and XCI. Here, we have identified the pluripotency factor REX1 as a key target of RNF12 in the XCI mechanism. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout mouse ESCs show an increased level of REX1. Using ChIP-seq, REX1 binding sites were detected in Xist and Tsix regulatory regions. Over-expression of REX1 in female ESCs was found to inhibit Xist transcription and XCI, whereas male Rex1+/- ESCs showed ectopic XCI. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate XCI. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and XCI.
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| Overall design |
2 (one control one pulldown) samples
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| Contributor(s) |
Gribnau J, Gontan C, Achame EM, van IJcken W, Grootegoed JA |
| Citation(s) |
22596162 |
| Submission date |
Mar 10, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Eskeatnaf Mulugeta Achame |
| E-mail(s) |
e.mulugetaachame@erasmusmc.nl
|
| Phone |
0031614883537
|
| URL |
http://www.erasmusmc.nl/rede/
|
| Organization name |
Erasmusmc
|
| Department |
Reproduction and Development
|
| Lab |
Reproduction and Development
|
| Street address |
Dr Molewaterplein 50
|
| City |
Rotterdam |
| State/province |
Rotterdam |
| ZIP/Postal code |
3015 GE |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (2) |
|
| Relations |
| SRA |
SRP011405 |
| BioProject |
PRJNA153217 |
