Trans-chromosomal regulation by a novel lincRNA required for adipogenesis that escapes X-chromosome inactivation

Long noncoding RNAs (lncRNAs) have emerged as an important layer of genome regulation with common mechanistic themes including the formation of ribonucleoprotein complexes. Here, we present a novel X-linked lncRNA termed linc-Firre that escapes X-chromosome inactivation and forms trans-chromosomal interactions required for adipogenesis. Linc-Firre is exclusively nuclear and forms punctate expression foci on chromatin near its site of transcription on both X-chromosomes in human and mouse. Both the localization of linc-Firre and the association with the nuclear matrix protein hnRNPU require a conserved repeating RNA domain, R2D2. Collectively, these results reveal a lincRNA that escapes X-chromosome inactivation with a critical role in driving cell fate decisions by trans-chromosomal interactions. Overall design: Replicate RNA-Seq analyses of oligo-mediated knockdowns of linc-FIRRE and hnRNPU in two different cellular contexts; HeLa cells and mouse embryonic stem cells. Also included are Firre knockout and wild-type mouse embryonic stem cells.