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

Friedmann Loos; Cheryl Maduro; Agnese Loda; Johannes Lehmann; Gert-Jan Kremers; Derk Berge; Anton Grootegoed; Joost Gribnau

doi:10.1128/MCB.00183-16

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

Friedmann Loos, Cheryl Maduro, Agnese Loda, Johannes Lehmann, Gert-Jan Kremers, Derk Berge, Anton Grootegoed, Joost Gribnau

Research output: Contribution to journal › Article › Academic › peer-review

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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 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.

Original language	Undefined/Unknown
Pages (from-to)	2656-2667
Number of pages	12
Journal	Molecular and Cellular Biology
Volume	36
Issue number	21
DOIs	https://doi.org/10.1128/MCB.00183-16
Publication status	Published - 2016

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EMC MGC-02-13-02
EMC MGC-02-82-01

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10.1128/MCB.00183-16

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Cite this

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title = "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 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.",

author = "Friedmann Loos and Cheryl Maduro and Agnese Loda and Johannes Lehmann and Gert-Jan Kremers and Derk Berge and Anton Grootegoed and Joost Gribnau",

year = "2016",

doi = "10.1128/MCB.00183-16",

language = "Undefined/Unknown",

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pages = "2656--2667",

journal = "Molecular and Cellular Biology",

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T1 - Xist and Tsix Transcription Dynamics Is Regulated by the X-to-Autosome Ratio and Semistable Transcriptional States

AU - Loos, Friedmann

AU - Maduro, Cheryl

AU - Loda, Agnese

AU - Lehmann, Johannes

AU - Kremers, Gert-Jan

AU - Berge, Derk

AU - Grootegoed, Anton

AU - Gribnau, Joost

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1128/MCB.00183-16

DO - 10.1128/MCB.00183-16

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JO - Molecular and Cellular Biology

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