The lincRNA Pantr1 is a FOXG1 target gene conferring site-specific chromatin binding of FOXG1

Derailed gene expression programs within the developing nervous system, encompassing both transcriptional and post-transcriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNA Pantr1. We identified FOXG1 as an upstream transcriptional activator of Pantr1 in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both transcriptional regulation of Pantr1 by FOXG1 and binding of both partners build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically, Pantr1 facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, and Pantr1 reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression of Pantr1 underlines the importance of the FOXG1/Pantr1 regulative network.