biostudies-literatureLi ENational Eye Research CentreU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)NIA NIH HHSU.S. Department of Health &amp; Human Services | NIH | National Institute on AgingNIMH NIH HHSNational Eye Research Centre (NERC)U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)U.S. Department of Health &amp; Human Services | NIH | National Institute of Mental Health6902https://www.ebi.ac.uk/biostudies/studies/S-EPMC12297475biostudies-literatureUnknown16(1)During mouse embryonic brain development, the Evf2 ultraconserved enhancer (UCE) lncRNA guides the Dlx5/6UCE to ~129 sites across chr6. However, previous work identified only 4 transcriptionally regulated targets associated with Evf2-Dlx5/6UCE-gene guidance, raising questions about the significance of Evf2-regulated Dlx5/6UCE-gene interactions. Here, single-cell transcriptomics reveal far greater alignment between Evf2-Dlx5/6UCE-gene guidance and transcriptional regulation than previously reported. Evf2 divides chr6 into short-range ( <10 Mb distant), activated genes, and long/super-long-range (10-129 Mb distant), repressed genes, identifying seizure regulating genes in the embryonic subventricular zone that predict adult phenotypes. Evf2-regulated Dlx5/6UCE-gene distances and directions (Nature communicationsSingle-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains.PMC12297475R01MH111267R03MH126145R03 MH126145P30EY002687RF1 AG068140RF1AG068140R01 MH111267Cajigas IAy FKohtz SJHinojosa-Gonzalez LLi EVassar RJChakraborty AShiau FBertossi RClark BSKessler JAKohtz JDfalseSingle-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains.During mouse embryonic brain development, the Evf2 ultraconserved enhancer (UCE) lncRNA guides the Dlx5/6UCE to ~129 sites across chr6. However, previous work identified only 4 transcriptionally regulated targets associated with Evf2-Dlx5/6UCE-gene guidance, raising questions about the significance of Evf2-regulated Dlx5/6UCE-gene interactions. Here, single-cell transcriptomics reveal far greater alignment between Evf2-Dlx5/6UCE-gene guidance and transcriptional regulation than previously reported. Evf2 divides chr6 into short-range ( <10 Mb distant), activated genes, and long/super-long-range (10-129 Mb distant), repressed genes, identifying seizure regulating genes in the embryonic subventricular zone that predict adult phenotypes. Evf2-regulated Dlx5/6UCE-gene distances and directions (2025-01-01T00:00:00Z2025 Jul2026-07-15T09:44:01.878Z2025-08-28T03:09:18.489ZS-EPMC122974754071514410.1038/s41467-025-62205-y