Maéva Langouët

Maéva Langouët photo

Project Title: 

Reactivation of 15q11.2-q13 maternal genes in PWS-specific neurons derived from iPSCs by targeting ZNF274: a potential target for future therapeutic applications

Host Organisation: 

University of Connecticut Health Center / Genetics and Genome Sciences

Short biography

Feb. 2015 – present
Department of Genetics and Genome Sciences, School of Medicine, University of Connecticut, Farmington, CT (USA)
Reactivation of 15q11.2-q13 maternal genes in PWS-specific neurons derived from iPSCs by targeting ZNF274: a potential target for future therapeutic applications
Postdoctoral fellowship in Dr. Marc Lalande’s group

Oct. 2011 – Dec 2014
INSERM UMR 1163, Imagine Institute, Necker-Enfants Malades hospital, Paris (France)
Deciphering the molecular bases of intellectual disabilities and understanding of relevant pathophysiological mechanisms, in the era of high-throughput sequencing
PhD thesis advised by Dr. Laurence Colleaux

Jan. 2011 - Sept. 2011
INSERM U781, Necker- Enfants Malades hospital, Paris (France)
Contribution to the identification of genes whose mutations are responsible for autosomal recessive forms of intellectual deficiencies
9-months internship in Dr. Laurence Colleaux’s group

Apr. 2010 -Aug. 2010
Fred Hutchinson Cancer Research Center, Seattle (USA)
Identification and characterization of microchimeric cells in lung tissue of Systemic Sclerosis patients
5-months internship in Dr. J. Lee Nelson’s laboratory

Jun. 2009 - Aug. 2009
Institute of Zoology in the University of Zurich, Zurich (Switzerland)
Study of the expression pattern of the EGF Receptor gene at different stages of development in C. elegans
3 months internship in Alex Hajnal’s laboratory

Brief description of research project

Prader-Willi syndrome (PWS) is a neurobehavioural disorder of genomic imprinting and is characterised by neonatal hypotonia and, subsequently, by hyperphagia and consequent obesity as well as behavioural problems. PWS is caused by the absence of a normal paternal contribution to chromosome 15q11-q13. The PWS-Imprinting Center (PWS-IC), a region of differential CpG methylation is known to control imprinting at this region. In brain, a paternally expressed long non-coding RNA (PWS IncRNA) initiates upstream of the PWS-IC and extends >600kb distally to overlap and repress the paternal allele of UBE3A. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zing-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. We have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-IC. This suggests that the ZNF274 complex is a separate imprinting mark that represses maternal PWS gene expression in neurons and is a potential target for future therapeutic applications to rscue the PWS phenotype.