LINE-1 retrotransposons contribute to mouse PV interneuron development

• Published in: Nature neuroscience 2024-07, Vol.27 (7), p.1274-1284
• Main Authors: Bodea, Gabriela O., Botto, Juan M., Ferreiro, Maria E., Sanchez-Luque, Francisco J., de los Rios Barreda, Jose, Rasmussen, Jay, Rahman, Muhammed A., Fenlon, Laura R., Jansz, Natasha, Gubert, Carolina, Gerdes, Patricia, Bodea, Liviu-Gabriel, Ajjikuttira, Prabha, Da Costa Guevara, Darwin J., Cumner, Linda, Bell, Charles C., Kozulin, Peter, Billon, Victor, Morell, Santiago, Kempen, Marie-Jeanne H. C., Love, Chloe J., Saha, Karabi, Palmer, Lucy M., Ewing, Adam D., Jhaveri, Dhanisha J., Richardson, Sandra R., Hannan, Anthony J., Faulkner, Geoffrey J.
• Format: Article
• Language: English
• Subjects: 13/31; 13/51; 14; 14/32; 38; 38/91; 42; 45/23; 631/208/212/177; 631/378/1697/1691; 631/378/2571/1696; 631/378/2583; 82; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Deoxyribonucleic acid; DNA; DNA methylation; Gene duplication; Gene expression; Gene Expression Regulation, Developmental - genetics; Gene sequencing; Genes; Interneurons; Interneurons - metabolism; Interneurons - physiology; Long interspersed nucleotide elements; Long Interspersed Nucleotide Elements - genetics; Male; Mice; Mice, Inbred C57BL; Neurobiology; Neurogenesis - genetics; Neurogenesis - physiology; Neurons; Neurosciences; Nucleotide sequence; Parvalbumin; Parvalbumins - metabolism; Proteins; Regulatory sequences; Retroelements - genetics; Reverse transcription; Transcription activation; Transcription factors; Transcriptomes
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-024-01650-2

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis -regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineages or therein promote neurodevelopmental gene expression. Here we report programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV) interneuron development. Mouse PV interneurons permit L1 mobilization in vitro and in vivo, harbor unmethylated L1 promoters and express full-length L1 mRNAs and proteins. Using nanopore long-read sequencing, we identify unmethylated L1s proximal to PV interneuron genes, including a novel L1 promoter-driven Caps2 transcript isoform that enhances neuron morphological complexity in vitro. These data highlight the contribution made by L1 cis -regulatory elements to PV interneuron development and transcriptome diversity, uncovered due to L1 mobility in this milieu. LINE-1 retrotransposons are a type of mobile DNA element normally repressed in the body. Here the authors show that LINE-1 sequences can jump in mouse parvalbumin interneurons and also promote the transcription of key parvalbumin interneuron genes.