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Series GSE36417 Query DataSets for GSE36417
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.
Overall design 2 (one control one pulldown) samples
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
Phone 0031614883537
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
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM892957 Wild type
GSM892958 V5-tagged REX1 pulldown
SRA SRP011405
BioProject PRJNA153217

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Supplementary file Size Download File type/resource
GSE36417_RAW.tar 563.8 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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