The Evf2 Ultraconserved Enhancer lncRNA Functionally and Spatially Organizes Megabase Distant Genes in the Developing Forebrain.

Gene regulation requires selective targeting of DNA regulatory enhancers over megabase distances. Here we show that Evf2, a cloud-forming Dlx5/6 ultraconserved enhancer (UCE) lncRNA, simultaneously localizes to activated (Umad1, 1.6 Mb distant) and repressed (Akr1b8, 27 Mb distant) chr6 target genes, precisely regulating UCE-gene distances and cohesin binding in mouse embryonic forebrain GABAergic interneurons (INs).

A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import.

Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE.

The roles of the DAZ family in spermatogenesis: More than just translation?

The DAZ family of genes are important fertility factors in animals, including humans. The family consists of Y-linked DAZ, and autosomal homologs Boule and Dazl. All three genes encode RNA-binding proteins that are nearly exclusively expressed in germ cells.

Widespread presence of human BOULE homologs among animals and conservation of their ancient reproductive function.

Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive evolution they often become divergent. Indeed out of hundreds of male or female fertility genes identified in diverse organisms, only a very small number of them are implicated specifically in reproduction in more than one lineage.

A novel requirement in mammalian spermatid differentiation for the DAZ-family protein Boule.

Reproduction is required for the survival of all animals, yet few reproductive genes have been shown to have a conserved requirement for fertility across the animal kingdom. Remarkably, the RNA binding protein BOULE, the oldest member of the DAZ (Deleted in AZoospermia) family of genes, appears to have maintained its conserved functional motif and spermatogenic expression from insects to humans. Boule mutations lead to a pachytene meiotic arrest before metaphase in Drosophila males and C.

Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry.

Genomic studies demonstrate that, although the majority of the mammalian genome is transcribed, only about 2% of these transcripts are code for proteins. We investigated how the long, polyadenylated Evf2 noncoding RNA regulates transcription of the homeodomain transcription factors DLX5 and DLX6 in the developing mouse forebrain. We found that, in developing ventral forebrain, Evf2 recruited DLX and MECP2 transcription factors to important DNA regulatory elements in the Dlx5/6 intergenic region and controlled Dlx5, Dlx6 and Gad1 expression through trans and cis-acting mechanisms.