title: Xist-dependent imprinted X inactivation and the early developmental consequences of its failure.
abstract: The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development. We also demonstrate that the expression dynamics of X-linked genes depends on the strain and parent of origin as well as on the location along the X chromosome, particularly at the first 'entry' sites of Xist. This study demonstrates that dosage-compensation failure has an effect as early as the blastocyst stage and reveals genetic and epigenetic contributions to orchestrating transcriptional silencing of the X chromosome during early embryogenesis.
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Maud
authors.identifier: 0000-0002-4378-5018
authors.initials: M
authors.lastname: Borensztein
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.|Institut Curie, PSL Research University, Mines Paris Tech, Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, F-75005, Paris, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Syx
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Katia
authors.identifier: 0000-0002-2117-9754
authors.initials: K
authors.lastname: Ancelin
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Diabangouaya
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Picard
authors.affiliation: Annoroad Gene Technology Co., Ltd, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Annoroad Gene Technology Co., Ltd, Beijing, China.
authors.forename: Jun-Bin
authors.initials: JB
authors.lastname: Liang
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.|Institut Curie, PSL Research University, Mines Paris Tech, Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, F-75005, Paris, France.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Vassilev
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Rafael
authors.identifier: 0000-0001-7319-043X
authors.initials: R
authors.lastname: Galupa
authors.affiliation: Institut Curie, PSL Research University, Mines Paris Tech, Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, F-75005, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Institut Curie, PSL Research University, Mines Paris Tech, Bioinformatics and Computational Systems Biology of Cancer, INSERM U900, F-75005, Paris, France.
authors.forename: Emmanuel
authors.identifier: 0000-0003-2724-2002
authors.initials: E
authors.lastname: Barillot
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Azim
authors.initials: A
authors.lastname: Surani
authors.affiliation: Annoroad Gene Technology Co., Ltd, Beijing, China.
authors.forename: Chong-Jian
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004303:Dosage Compensation, Genetic; D010064:Embryo Implantation / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D050172:Genes, X-Linked; D018392:Genomic Imprinting; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D013997:Time Factors; D014960:X Chromosome / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA