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- W4295693222 abstract "Allele-specific expression of imprinted gene clusters is governed by gametic DNA methylation at master regulators called imprinting control regions (ICRs). Non-gametic or secondary differentially methylated regions (DMRs) at promoters and exonic regions reinforce monoallelic expression but do not control an entire cluster. Here, we unveil an unconventional secondary DMR that is indispensable for tissue-specific imprinting of two previously unlinked genes, Grb10 and Ddc. Using polymorphic mice, we mapped an intronic secondary DMR at Grb10 with paternal-specific CTCF binding (CBR2.3) that forms contacts with Ddc. Deletion of paternal CBR2.3 removed a critical insulator, resulting in substantial shifting of chromatin looping and ectopic enhancer-promoter contacts. Destabilized gene architecture precipitated abnormal Grb10-Ddc expression with developmental consequences in the heart and muscle. Thus, we redefine the Grb10-Ddc imprinting domain by uncovering an unconventional intronic secondary DMR that functions as an insulator to instruct the tissue-specific, monoallelic expression of multiple genes-a feature previously ICR exclusive." @default.
- W4295693222 created "2022-09-14" @default.
- W4295693222 creator A5004404479 @default.
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- W4295693222 creator A5057280899 @default.
- W4295693222 creator A5068052931 @default.
- W4295693222 creator A5090359164 @default.
- W4295693222 date "2022-10-01" @default.
- W4295693222 modified "2023-10-14" @default.
- W4295693222 title "Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development" @default.
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