LINE-1 retrotransposons contribute to mouse PV interneuron development

Gabriela O Bodea; Juan M Botto; Maria E Ferreiro; Francisco J Sanchez-Luque; Jose de Los Rios Barreda; Jay Rasmussen; Muhammed A Rahman; Laura R Fenlon; Natasha Jansz; Carolina Gubert; Patricia Gerdes; Liviu-Gabriel Bodea; Prabha Ajjikuttira; Darwin J Da Costa Guevara; Linda Cumner; Charles C Bell; Peter Kozulin; Victor Billon; Santiago Morell; Marie-Jeanne H C Kempen; Chloe J Love; Karabi Saha; Lucy M Palmer; Adam D Ewing; Dhanisha J Jhaveri; Sandra R Richardson; Anthony J Hannan; Geoffrey J Faulkner

doi:10.1038/s41593-024-01650-2

LINE-1 retrotransposons contribute to mouse PV interneuron development

Gabriela O Bodea, Juan M Botto, Maria E Ferreiro, Francisco J Sanchez-Luque, Jose de Los Rios Barreda, Jay Rasmussen, Muhammed A Rahman, Laura R Fenlon, Natasha Jansz, Carolina Gubert, Patricia Gerdes, Liviu-Gabriel Bodea, Prabha Ajjikuttira, Darwin J Da Costa Guevara, Linda Cumner, Charles C Bell, Peter Kozulin, Victor Billon, Santiago Morell, Marie-Jeanne H C KempenChloe J Love, Karabi Saha, Lucy M Palmer, Adam D Ewing, Dhanisha J Jhaveri, Sandra R Richardson, Anthony J Hannan, Geoffrey J Faulkner

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1274-1284
Number of pages	34
Journal	Nature Neuroscience
Volume	27
Issue number	7
Early online date	2024 May 21
DOIs	https://doi.org/10.1038/s41593-024-01650-2
Publication status	Published - 2024
Externally published	Yes

Bibliographical note

Subject classification (UKÄ)

Neurosciences

Free keywords

Epigenomics
Genetics of the nervous system
Inhibition
Neuronal development

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Bodea, G. O., Botto, J. M., Ferreiro, M. E., Sanchez-Luque, F. J., de Los Rios Barreda, J., Rasmussen, J., Rahman, M. A., Fenlon, L. R., Jansz, N., Gubert, C., Gerdes, P., Bodea, L.-G., Ajjikuttira, P., Da Costa Guevara, D. J., Cumner, L., Bell, C. C., Kozulin, P., Billon, V., Morell, S., ... Faulkner, G. J. (2024). LINE-1 retrotransposons contribute to mouse PV interneuron development. Nature Neuroscience, 27(7), 1274-1284. https://doi.org/10.1038/s41593-024-01650-2

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title = "LINE-1 retrotransposons contribute to mouse PV interneuron development",

abstract = "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.",

keywords = "Epigenomics, Genetics of the nervous system, Inhibition, Neuronal development",

author = "Bodea, {Gabriela O} and Botto, {Juan M} and Ferreiro, {Maria E} and Sanchez-Luque, {Francisco J} and {de Los Rios Barreda}, Jose and Jay Rasmussen and Rahman, {Muhammed A} and Fenlon, {Laura R} and Natasha Jansz and Carolina Gubert and Patricia Gerdes and Liviu-Gabriel Bodea and Prabha Ajjikuttira and {Da Costa Guevara}, {Darwin J} and Linda Cumner and Bell, {Charles C} and Peter Kozulin and Victor Billon and Santiago Morell and Kempen, {Marie-Jeanne H C} and Love, {Chloe J} and Karabi Saha and Palmer, {Lucy M} and Ewing, {Adam D} and Jhaveri, {Dhanisha J} and Richardson, {Sandra R} and Hannan, {Anthony J} and Faulkner, {Geoffrey J}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

doi = "10.1038/s41593-024-01650-2",

language = "English",

volume = "27",

pages = "1274--1284",

journal = "Nature Neuroscience",

issn = "1546-1726",

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Bodea, GO, Botto, JM, Ferreiro, ME, Sanchez-Luque, FJ, de Los Rios Barreda, J, Rasmussen, J, Rahman, MA, Fenlon, LR, Jansz, N, Gubert, C, Gerdes, P, Bodea, L-G, Ajjikuttira, P, Da Costa Guevara, DJ, Cumner, L, Bell, CC, Kozulin, P, Billon, V, Morell, S, Kempen, M-JHC, Love, CJ, Saha, K, Palmer, LM, Ewing, AD, Jhaveri, DJ, Richardson, SR, Hannan, AJ & Faulkner, GJ 2024, 'LINE-1 retrotransposons contribute to mouse PV interneuron development', Nature Neuroscience, vol. 27, no. 7, pp. 1274-1284. https://doi.org/10.1038/s41593-024-01650-2

TY - JOUR

T1 - LINE-1 retrotransposons contribute to mouse PV interneuron development

AU - Bodea, Gabriela O

AU - Botto, Juan M

AU - Ferreiro, Maria E

AU - Sanchez-Luque, Francisco J

AU - de Los Rios Barreda, Jose

AU - Rasmussen, Jay

AU - Rahman, Muhammed A

AU - Fenlon, Laura R

AU - Jansz, Natasha

AU - Gubert, Carolina

AU - Gerdes, Patricia

AU - Bodea, Liviu-Gabriel

AU - Ajjikuttira, Prabha

AU - Da Costa Guevara, Darwin J

AU - Cumner, Linda

AU - Bell, Charles C

AU - Kozulin, Peter

AU - Billon, Victor

AU - Morell, Santiago

AU - Kempen, Marie-Jeanne H C

AU - Love, Chloe J

AU - Saha, Karabi

AU - Palmer, Lucy M

AU - Ewing, Adam D

AU - Jhaveri, Dhanisha J

AU - Richardson, Sandra R

AU - Hannan, Anthony J

AU - Faulkner, Geoffrey J

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Epigenomics

KW - Genetics of the nervous system

KW - Inhibition

KW - Neuronal development

U2 - 10.1038/s41593-024-01650-2

DO - 10.1038/s41593-024-01650-2

M3 - Article

C2 - 38773348

SN - 1546-1726

VL - 27

SP - 1274

EP - 1284

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 7

ER -

LINE-1 retrotransposons contribute to mouse PV interneuron development

Abstract

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