PRBB-CRG Sessions Amanda Whipple

27/03/202612:00MARIE CURIEPRBB-CRG SessionsAmanda WhippleHarvard University"Mechanisms of Imprinted Gene Regulation in the Brain"Host: Postdoc CommunityAbstract:Genomic imprinting is an epigenetic process that drives parent-of-origin–specific gene expression and is essential for brain development. Disruption of imprinting causes severe neurodevelopmental disorders, including Angelman and Prader–Willi syndromes. However, the mechanisms that establish and maintain allele-specific expression in neural cells remain incompletely understood.
Our lab investigates how chromatin architecture and noncoding RNAs regulate imprinted genes in the developing brain. Using allele-specific chromatin conformation approaches in hybrid mouse models, we find that differentially methylated regions anchor parent-specific 3D genome organization across imprinted domains. At the Peg13–Kcnk9 locus, CTCF-dependent chromatin structure preconfigures enhancer interactions that prime allele-specific gene activation during neurogenesis.

In parallel, we study imprinted small nucleolar RNAs within the Prader–Willi syndrome locus. Mapping RNA–target interactions in neurons reveals a functional interaction between Snord116 and rRNA that modulates translation of specific mRNAs, uncovering a link between imprinting and translational control.

Together, our work shows how allele-specific genome architecture and regulatory RNAs cooperate to shape gene expression in the brain and provides mechanistic insight into imprinting disorders.