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

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 upre...

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Bibliographic Details
Published in:Molecular and cellular biology 2016-11, Vol.36 (21), p.2656-2667
Main Authors: Loos, Friedemann, Maduro, Cheryl, Loda, Agnese, Lehmann, Johannes, Kremers, Gert-Jan, ten Berge, Derk, Grootegoed, J. Anton, Gribnau, Joost
Format: Article
Language:English
Subjects:
Alleles
Animals
Cell Line
Chromosomes, Mammalian - genetics
Female
Gene Expression Regulation
Gene Regulatory Networks
Genes, Reporter
Genetic Loci
Mice
Models, Genetic
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Transcription, Genetic
X Chromosome - genetics
X Chromosome Inactivation - genetics
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Summary: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 upregulation results in the 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 semistable transcriptional states of the Xic locus 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.
ISSN:1098-5549
0270-7306
1098-5549
DOI:10.1128/MCB.00183-16