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.
authors.affiliation: Department of Developmental Biology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Loos
authors.affiliation: Department of Developmental Biology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Maduro
authors.affiliation: Department of Developmental Biology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Agnese
authors.initials: A
authors.lastname: Loda
authors.affiliation: Erasmus MC Stem Cell Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Optical Imaging Center, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Kremers
authors.affiliation: Erasmus MC Stem Cell Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Derk
authors.initials: D
authors.lastname: Ten Berge
authors.affiliation: Department of Developmental Biology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: J Anton
authors.initials: JA
authors.lastname: Grootegoed
authors.affiliation: Department of Developmental Biology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands j.gribnau@erasmusmc.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: Gribnau
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D056426:Genetic Loci; D051379:Mice; D008957:Models, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA