26/01/2026 - Benoît MOINDROT : Un génome, Deux voix : Décodage des régulations chromatiniennes, et de leur perturbation, au sein des domaines soumis à l’empreinte parentale

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 11h–12h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 26 JANVIER 2026

One genome, two Voices: Decoding allelic chromatin-regulatory layers, and their perturbations, at imprinted domains

Benoît MOINDROT

Institut de Biologie Intégrative de la Cellule (I2BC)

Invited by Irène NETCHINE team Irène NETCHINE (irene.netchine@aphp.fr)

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imprinting is an epigenetic mechanism controlling the parent-of-origin–specific expression of ~200 genes in eutherian mammals. Its disruption can lead to developmental disorders, like Silver-Russell Syndrome (SRS).

Allelic gene regulation at imprinted domains is primarily established by DNA methylation at Differentially Methylated Regions (DMRs), followed by a cascade of epigenetic modifications acting on only one of the two alleles. These include the expression of regulatory non-coding RNAs, the deposition of specific histone marks, as well as the formation of distinct 3D chromatin architecture.

Using a multi-omics approach combined with targeted sequencing, I characterized the chromatin landscape of the imprinted Dlk1-Dio3 locus in mouse. I showed that a maternal-specific CTCF site structures active chromatin domains on the maternal allele, whereas the largely silenced paternal allele alternates between Polycomb- or lamina-mediated repression.

I have also analyzed the IGF2-H19 imprinted domain and its perturbation in cells derived from SRS patients. I demonstrated that hypomethylation at the H19-DMR in SRS rewires the chromatin architecture, causing the paternal allele to adopt a maternal-like conformation. This provides the first mechanistic insights into how imprinting defects perturb gene regulatory programs, through altered 3D-chromatin organization.