skip to primary navigationskip to content

30.01.17 Surani lab with Institut Curie colleagues probe Xist-mediated gene silencing in early embryogenesis

last modified Jan 30, 2017 05:35 PM
Analysing Xist-mutant embryos down to single-cell RNA sequencing, the Surani and Heard (Institut Curie) labs examine the epigenetic process of X-chromosome inactivation
30.01.17 Surani lab with Institut Curie colleagues probe Xist-mediated gene silencing in early embryogenesis

From Suppl. Fig 3a: Production of Xist RNA (green) in 16-cell stage female mouse embryos

Xist-dependent imprinted X inactivation and the early developmental consequences of its failure


M. Borensztein et al. (2017) Nature Structural & Molecular Biology DOI:10.1038/nsmb.3365

[Advance Online Publication Monday 30 January 2017]


Lead author Maud Borensztein explains: "In this paper, we describe the requirements and timing of X inactivation during pre-implantation embryogenesis, as well as the molecular events that occur when it fails, using single cell, allele-specific RNA sequencing of embryos derived from mice with polymorphic X chromosomes.

Our single cell in vivo data reveals that in Xist-mutant embryos, there are major perturbation of both extraembryonic development and pluripotency pathways, detected as early as the blastocyst stage, several days before the death of the embryo, following implantation.

We also uncover some unexpected actors involved this mis-regulation, including the imprinted, X-linked Rhox5 gene. This paper provides many novel insights into Xist lncRNA-mediated gene silencing and epigenetic events in a developmental context."

Abstract from the paper 

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.


Read more about research in the Surani lab.

Hear Maud Borensztein answer listeners' questions, such as 'How much does a cell weigh?' in this Naked Scientists podcast.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

combinedLogo x3 trans2018


Share this

scmap: projection of single-cell RNA-seq data across data sets

Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis

Map of synthetic rescue interactions for the Fanconi anemia DNA repair pathway identifies USP48

The developmental origin of brain tumours: a cellular and molecular framework

Bioinformatics challenges and perspectives when studying the effect of epigenetic modifications on alternative splicing

ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks

Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer's Disease Disrupt Synaptic Plasticity

Combinational Treatment of Trichostatin A and Vitamin C Improves the Efficiency of Cloning Mice by Somatic Cell Nuclear Transfer

Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Validating the concept of mutational signatures with isogenic cell models

A PAX5-OCT4-PRDM1 developmental switch specifies human primordial germ cells

Targeting NAT10 enhances healthspan and lifespan in a mouse model of human accelerated aging syndrome

An alternative mode of epithelial polarity in the Drosophila midgut

Detection of functional protein domains by unbiased genome-wide forward genetic screening

Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium

Genome organization at different scales: nature, formation and function

Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations


Link to full list on PubMed