Xist and Tsix Transcription Dynamics Is Regulated by the X-to-Autosome Ratio and Semistable Transcriptional States

Abstract

In female mammals, X chromosome inactivation (XCI) is a key process in the control of gene dosage compensation between X-linked genes and autosomes. Xist and Tsix, two overlapping antisense transcribed noncoding genes, are central elements of the X inactivation center ( Xic) regulating XCI. Xist up-regulation results in coating of the entire X chromosome by Xist RNA in cis, whereas Tsix transcription acts as a negative regulator of Xist. Here, we generated Xist and Tsix reporter mouse embryonic stem (ES) cell lines, to study the genetic and dynamic regulation of these genes upon differentiation. Our results revealed mutually antagonistic roles for Tsix on Xist and vice versa, and indicate the presence of semi-stable transcriptional states of the Xic predicting the outcome of XCI. These transcriptional states are instructed by the X to autosome ratio, directed by regulators of XCI, and can be modulated by tissue culture conditions.