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LINE-1 retrotransposons contribute to mouse PV interneuron development

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 and Gubert, Carolina , et al. (2024) In Nature Neuroscience
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Epigenomics, Genetics of the nervous system, Inhibition, Neuronal development
in
Nature Neuroscience
pages
34 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:38773348
  • scopus:85193718920
ISSN
1546-1726
DOI
10.1038/s41593-024-01650-2
language
English
LU publication?
no
additional info
© 2024. The Author(s).
id
8ef35005-b85b-40b3-a9ec-504d7c75fd73
date added to LUP
2024-06-10 15:16:27
date last changed
2024-06-12 15:28:37
@article{8ef35005-b85b-40b3-a9ec-504d7c75fd73,
  abstract     = {{<p>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.</p>}},
  author       = {{Bodea, Gabriela O and Botto, Juan M and Ferreiro, Maria E and Sanchez-Luque, Francisco J and de Los Rios Barreda, Jose and Rasmussen, Jay and Rahman, Muhammed A and Fenlon, Laura R and Jansz, Natasha and Gubert, Carolina and Gerdes, Patricia and Bodea, Liviu-Gabriel and Ajjikuttira, Prabha and Da Costa Guevara, Darwin J and Cumner, Linda and Bell, Charles C and Kozulin, Peter and Billon, Victor and Morell, Santiago and Kempen, Marie-Jeanne H C and Love, Chloe J and Saha, Karabi and Palmer, Lucy M and Ewing, Adam D and Jhaveri, Dhanisha J and Richardson, Sandra R and Hannan, Anthony J and Faulkner, Geoffrey J}},
  issn         = {{1546-1726}},
  keywords     = {{Epigenomics; Genetics of the nervous system; Inhibition; Neuronal development}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Neuroscience}},
  title        = {{LINE-1 retrotransposons contribute to mouse PV interneuron development}},
  url          = {{http://dx.doi.org/10.1038/s41593-024-01650-2}},
  doi          = {{10.1038/s41593-024-01650-2}},
  year         = {{2024}},
}