LINE-1 retrotransposons contribute to mouse PV interneuron development

被引：1

作者：

Bodea, Gabriela O. ^{[1
,2
]}

Botto, Juan M. ^{[1
]}

Ferreiro, Maria E. ^{[1
]}

Sanchez-Luque, Francisco J. ^{[3
]}

Barreda, Jose de los Rios ^{[1
]}

Rasmussen, Jay ^{[1
]}

Rahman, Muhammed A. ^{[1
]}

Fenlon, Laura R. ^{[1
]}

Jansz, Natasha ^{[2
]}

Gubert, Carolina ^{[4
]}

Gerdes, Patricia ^{[2
]}

Bodea, Liviu-Gabriel ^{[5
]}

Ajjikuttira, Prabha ^{[1
]}

Guevara, Darwin J. Da Costa ^{[1
,2
]}

Cumner, Linda ^{[1
]}

Bell, Charles C. ^{[2
]}

Kozulin, Peter ^{[1
]}

Billon, Victor ^{[1
,6
]}

Morell, Santiago ^{[2
,10
]}

Kempen, Marie-Jeanne H. C. ^{[7
]}

Love, Chloe J. ^{[4
]}

Saha, Karabi ^{[8
]}

Palmer, Lucy M. ^{[4
,9
]}

Ewing, Adam D. ^{[2
]}

Jhaveri, Dhanisha J. ^{[1
,2
]}

Richardson, Sandra R. ^{[2
]}

Hannan, Anthony J. ^{[4
]}

Faulkner, Geoffrey J. ^{[1
,2
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[2] Univ Queensland, Mater Res Inst, TRI Bldg, Woolloongabba, Qld, Australia

[3] Spanish Natl Res Council, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[4] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia

[5] Univ Queensland, Queensland Brain Inst, Clem Jones Ctr Ageing Dementia Res, Brisbane, Qld, Australia

[6] Ecole Normale Super Paris Saclay, Biol Dept, Gif Sur Yvette, France

[7] Univ Edinburgh, Western Gen Hosp, Inst Genet & Canc, MRC Human Genet Unit, Edinburgh, Scotland

[8] South Dakota State Univ, Dept Pharmaceut Sci, Brookings, SD USA

[9] Univ Melbourne, Florey Dept Neurosci & Mental Hlth, Parkville, Vic, Australia

[10] Univ Cambridge, Dept Genet, Cambridge, England

来源：

NATURE NEUROSCIENCE | 2024年 / 27卷 / 07期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会;

关键词：

HUMAN L1 RETROTRANSPOSITION; CELLS; TRANSCRIPTION; METHYLATION; ELEMENT; FAMILY; DNA; EXPRESSION; DIVERSITY; MECHANISM;

D O I：

10.1038/s41593-024-01650-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1274 / 1284

页数：11

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