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



Rengifo Rojas, Cecilia, Cercy, Jil, Perillous, Sophie, Gonthier-Guéret, Céline, Montibus, Bertille, Maupetit-Méhouas, Stéphanie, Espinadel, Astrid, Dupré, Marylou, Hong, Charles C, Hata, Kenichiro
et al (show 6 more authors) (2024) Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment. Human Genetics and Genomics Advances, 5 (2). p. 100271.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Animals, Mice, DNA Methylation, Genomic Imprinting, Alleles, Promoter Regions, Genetic
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 16 Feb 2024 08:28
Last Modified: 20 Apr 2024 02:15
DOI: 10.1016/j.xhgg.2024.100271
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3178675