In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompassing sequence 5 KB upstream of the promoter through exon 3. We found that this mutation results in primary nonrandom X inactivation in which the wild-type X chromosome is always chosen for inactivation. To understand the molecular mechanisms that affect choice, we analyzed the role of replication timing in X inactivation choice. We found that the two Xist alleles and all regions tested on the X chromosome replicate asynchronously before the start of X inactivation. However, analysis of replication timing in cell lines with skewed X inactivation showed no preference for one of the two Xist alleles to replicate early in S-phase before the onset of X inactivation, indicating that asynchronous replication timing does not play a role in skewing of X inactivation.

dx.doi.org/10.1083/jcb.200405117, hdl.handle.net/1765/59383
The Journal of Cell Biology
Biophysical Genomics, Department Cell Biology & Genetics

Gribnau, J.H, Luikenhuis, S, Hochedlinger, K, Monkhorst, K, & Jaenisch, R. (2005). X chromosome choice occurs independently of asynchronous replication timing. The Journal of Cell Biology, 168(3), 365–373. doi:10.1083/jcb.200405117