Biallelic non-productive enhancer-promoter interaction precedes imprinted expression of<i>Kcnk9</i>during mouse neural commitment



Rojas, Cecilia Rengifo, Cercy, Jil, Perillous, Sophie, Gonthier-Guéret, Céline, Montibus, Bertille, Maupetit-Méhouas, Stéphanie, Espinadel, Astrid, Dupré, Marylou, Hong, Charles ORCID: 0000-0002-0424-8252, Hata, Kenichiro
et al (show 6 more authors) (2023) Biallelic non-productive enhancer-promoter interaction precedes imprinted expression of<i>Kcnk9</i>during mouse neural commitment. [Preprint]

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Abstract

How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood. To gain insight into the regulation of the Peg13-Kcnk9 domain, an imprinted domain with important brain functions, during neural commitment, we performed an integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression during neurodevelopment. We evidence that despite an allelic higher-order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, the enhancer- Kcnk9 promoter contacts can occur on both alleles, although they are only productive 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: Preprint
Uncontrolled Keywords: Genetics, Stem Cell Research, Neurosciences, Stem Cell Research - Nonembryonic - Non-Human, 1 Underpinning research, 2 Aetiology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance
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: 20 Oct 2023 09:35
Last Modified: 23 Mar 2024 04:01
DOI: 10.1101/2023.09.26.559498
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3174618