The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders [lnc-Nr2f1 overexpression]
ABSTRACT: The goal is to examine the global transcriptomic changes upon lnc-Nr2f1 overexpression in human neuroblastoma cells Overall design: Examination of global transcriptional changes and genome wide binding events of lnc-Nr2f1
Project description:Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.
Project description:The goal is to examine the global transcriptomic changes upon lnc-Nr2f1 overexpression in both Control and lnc-Nr2f1 KO ES cells. Overall design: Examination of global transcriptional changes and genome wide binding events of lnc-Nr2f1