Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment
Cecilia Rengifo Rojas,
Jil Cercy,
Sophie Perillous,
Céline Gonthier-Guéret,
Bertille Montibus,
Stéphanie Maupetit-Méhouas,
Astrid Espinadel,
Marylou Dupré,
Charles C. Hong,
Kenichiro Hata,
Kazuhiko Nakabayashi,
Antonius Plagge,
Tristan Bouschet,
Philippe Arnaud,
Isabelle Vaillant,
Franck Court
Affiliations
Cecilia Rengifo Rojas
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Jil Cercy
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Sophie Perillous
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Céline Gonthier-Guéret
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Bertille Montibus
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Stéphanie Maupetit-Méhouas
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Astrid Espinadel
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Marylou Dupré
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France
Charles C. Hong
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Kenichiro Hata
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan; Department of Human Molecular Genetics, Gunma University Graduate School of Medicine 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan
Kazuhiko Nakabayashi
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan
Antonius Plagge
Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
Tristan Bouschet
Institut de Génomique Fonctionnelle, CNRS, INSERM, Université de Montpellier, Montpellier, France
Philippe Arnaud
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France; Corresponding author
Isabelle Vaillant
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France; Corresponding author
Franck Court
Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France; Corresponding author
Summary: It is only partially understood how constitutive allelic methylation at imprinting control regions (ICRs) interacts with other regulation levels to drive timely parental allele-specific expression along large imprinted domains. The Peg13-Kcnk9 domain is an imprinted domain with important brain functions. To gain insights into its regulation during neural commitment, we performed an integrative analysis of its allele-specific epigenetic, transcriptomic, and cis-spatial organization using a mouse stem cell-based corticogenesis model that recapitulates the control of imprinted gene expression during neurodevelopment. We found that, despite an allelic higher-order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts occurred on both alleles, although they were productive only on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side and suggests a more nuanced role for allelic CTCF binding at some ICRs.