|Title||The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Barakat TStefan, Loos F, van Staveren S, Myronova E, Ghazvini M, J Grootegoed A, Gribnau J|
|Date Published||2014 Mar 20|
|Keywords||Animals, Biological Transport, Cell Line, Chromosome Pairing, Embryonic Stem Cells, Female, Gene Expression Regulation, Developmental, Humans, Mice, Knockout, RNA, Long Noncoding, Signal Transduction, Ubiquitin-Protein Ligases, X Chromosome, X Chromosome Inactivation|
X chromosome inactivation (XCI) in female placental mammals is a vital mechanism for dosage compensation between X-linked and autosomal genes. XCI starts with activation of Xist and silencing of the negative regulator Tsix, followed by cis spreading of Xist RNA over the future inactive X chromosome (Xi). Here, we show that XCI does not require physical contact between the two X chromosomes (X-pairing) but is regulated by trans-acting diffusible factors. We found that the X-encoded trans-acting and dose-dependent XCI-activator RNF12 acts in concert with the cis-regulatory region containing Jpx, Ftx, and Xpr to activate Xist and to overcome repression by Tsix. RNF12 acts at two subsequent steps; two active copies of Rnf12 drive initiation of XCI, and one copy needs to remain active to maintain XCI toward establishment of the Xi. This two-step mechanism ensures that XCI is very robust and fine-tuned, preventing XCI of both X chromosomes.
|Alternate Journal||Mol. Cell|