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Reprogrammation épigénétique et Développement

Maud Borensztein

Projets de recherche

 

Our group investigates X-chromosome reactivation during the specification of the germline. This female-specific reprogramming pathway is a paradigm of epigenetic resetting and fine gene-regulation control. A better understanding of the mechanisms involved in gene expression regulation and epigenetic memory is crucial, especially in the very unique context of the germ line formation.

Epigenetic memory plays a determinant role in locking cell fates through inheritance of chromatin modifications such as DNA methylation and histone marks. This is paramount for the stability of gene expression programs, cell identity and functions. In mammals, the most drastic transition in cell fate coincides with the emergence of the germline in the embryo. It involves a profound epigenetic remodelling of the cells. Occurring in both sexes, germline reprogramming is essential for the specialization of reproductive cells, and therefore, for the perpetuation of the species. However, in females specifically, reactivation of the entire inactive X chromosome, an epigenetic hallmark of female somatic cells, accompanies the acquisition of germline identity. Incidentally, this leads to a biallelic expression of X-linked gene in the germline precursors of XX females compared to XY males, at the onset of gonadal sex determination. The biological impact and significance of this sex-specific epigenetic characteristics is unknown. However, the presence of a non-reactivated X chromosome could be detrimental to homologous chromosome pairing and segregation in meiosis, and could lead to maternally inherited sex-chromosome aneuploidies such as XO and XXY syndromes in humans.

 

 

 

 

 

In the group, we aim to investigate the specificity and principles of female germline epigenetic reprogramming by :

1) Mapping the reshuffling of the epigenetic landscape on the active and inactive X chromosomes and in a sex-specific manner.

Techniques: mouse, cytometry, low-input CUT&RUN, ChIPseq, WGBS

2) Identifying the molecular mechanisms involved in X-chromosome reactivation in a culture-based system of germ cells.

Techniques: cell culture, mPGCLC, cytometry, RNAseq, CRISPR screen

3) Investigating the reciprocal influence between X-chromosome activity and global genome transcription.

Techniques: cell culture, mPGCLC, cell nornalized RNAseq, RNA-FISH

Ultimately, this work will have broader implications for sex-chromosome related infertility and aneuploidy syndromes, stem cell and reproductive medicine, as well as epigenetic inheritance and cancer.

 

Selection of publications :

Borensztein M*, Okamoto I*, Syx L, Guilbaud G, Picard C, Ancelin K, Galupa R, Diabangouaya P, Servant N, Barillot E, Surani A, Saitou M, Chen CJ, Anastassiadis K, Heard E. Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass. Nature Communications, 2017, 8 (1):1297; doi: 10.1038/s41467-017-01415-5.

Borensztein M, Syx L, Ancelin K, Diabangouya P, Picard C, Liu T, Liang JB, Vassilev Y, Galupa R, Servant N, Barillot E, Surani MA, Chen CJ, Heard E. Xist-dependent imprinted X inactivation and the early developmental consequences of its failure. Nature Structural and Molecular Biology, 2017, 24: 226-233; doi: 10.1038/nsmb.3365.

Zylicz JJ*, Borensztein M*, Wong FC, Huang Y, Lee C, Dietmann S, Surani MA. G9a regulates temporal preimplantation developmental program and lineage segregation in blastocysts. eLIFE, 2018, pii: e33361 ; doi: 10.7554/eLife.33361.

Borensztein M. Investigating the inner cell mass of the mouse blastocyst by combined immunofluorescence staining and RNA fluorescent in situ hybridization. Methods in Molecular Biology, 2020, doi:10.1007/978-1-0716-0958-3_11.

Borensztein M, Syx L, Servant N, Heard E. Transcriptome profiling of single mouse oocytes. Methods in Molecular Biology, 2018, 1818:51-65; doi: 10.1007/978-1-4939-8603-3_7.

List of all the publication :

https://pubmed.ncbi.nlm.nih.gov/?term=maud+borensztein&sort=date

Membres

Team leader

Maud BORENSZTEIN

Chercheur

+33 (0)4 34 35 97 28

111

Emmanuelle BEYNE

IR-Recherche

+33 (0)4 34 35 96 47

111

Karim CHEBLI

IR-Recherche

(+33) 04 34 35 96 47

111

Laurine JACOB

Stagiaire

+33 (0)4 34 35 96 47

11

Yolanda MOYANO-RODRIGUEZ

Post-Doc

+33 (0)4 34 35 96 46

111

Christel PICARD

IE-Recherche

+33 (0)4 34 35 96 46

111

Clara ROIDOR

Doctorant

+33 (0)4 34 35 96 47

RDC 03

Dominika ZURKOWSKA

IE-Recherche

+33 (0)4 34 35 96 47

111

Toutes les équipe de recherche

Mots-clés
Model organism studied
Mouse, embryonic stem cells, primordial germ cell like-cells
Biological process
Epigenetic reprogramming, X-chromosome reactivation, control of gene expression
Biological techniques
Single cell RNAseq, low-input epigenomics, bioinformatics, stem cell engineering MEDICAL APPLICATION reproduction, stem cell medicine, cancer