Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment.

HGG advances 2024 Apr 11

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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. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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. Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment. HGG advances. 2024 Apr 11;5(2):100271