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Article Dans Une Revue Human Genetics and Genomics Advances Année : 2024

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

Résumé

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.
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hal-04444966 , version 1 (07-02-2024)

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Cecilia Rengifo Rojas, Jil Cercy, Sophie Perillous, Céline Gonthier-Guéret, Bertille Montibus, et al.. Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment. Human Genetics and Genomics Advances, In press, pp.100271. ⟨10.1016/j.xhgg.2024.100271⟩. ⟨hal-04444966⟩
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