PT  - JOURNAL ARTICLE
AU  - Ya-Ping Yen
AU  - Wen-Fu Hsieh
AU  - Ya-Lin Lu
AU  - Ee Shan Liau
AU  - Ho-Chiang Hsu
AU  - Yen-Chung Chen
AU  - Ting-Chun Liu
AU  - Mien Chang
AU  - Joye Li
AU  - Shau-Ping Lin
AU  - Jui-Hung Hung
AU  - Jun-An Chen
TI  - <em>Dlk1-Dio3</em> Locus-Derived LncRNAs Perpetuate Postmitotic Motor Neuron Cell Fate and Subtype Identity
AID  - 10.1101/320135
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 320135
4099  - http://biorxiv.org/content/early/2018/05/11/320135.short
4100  - http://biorxiv.org/content/early/2018/05/11/320135.full
AB  - The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e. Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By transcriptome profiling cell types at each stage of spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Jarid2-Ezh2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data illustrate that these lncRNAs in the Dlk1-Dio3 locus play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes, providing strong evidence of how lncRNAs function during embryonic development.