Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
13
12
2020
accepted:
15
07
2021
pubmed:
18
8
2021
medline:
11
3
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
Transposable elements (TEs) account for more than 50% of the human genome and many have been co-opted throughout evolution to provide regulatory functions for gene expression networks. Several lines of evidence suggest that these networks are fine-tuned by the largest family of TE controllers, the KRAB-containing zinc finger proteins (KZFPs). One tissue permissive for TE transcriptional activation (termed "transposcription") is the adult human brain, however comprehensive studies on the extent of this process and its potential contribution to human brain development are lacking. To elucidate the spatiotemporal transposcriptome of the developing human brain, we have analyzed two independent RNA-seq data sets encompassing 16 brain regions from eight weeks postconception into adulthood. We reveal a distinct KZFP:TE transcriptional profile defining the late prenatal to early postnatal transition, and the spatiotemporal and cell type-specific activation of TE-derived alternative promoters driving the expression of neurogenesis-associated genes. Long-read sequencing confirmed these TE-driven isoforms as significant contributors to neurogenic transcripts. We also show experimentally that a co-opted antisense L2 element drives temporal protein relocalization away from the endoplasmic reticulum, suggestive of novel TE dependent protein function in primate evolution. This work highlights the widespread dynamic nature of the spatiotemporal KZFP:TE transcriptome and its importance throughout TE mediated genome innovation and neurotypical human brain development. To facilitate interactive exploration of these spatiotemporal gene and TE expression dynamics, we provide the "Brain TExplorer" web application freely accessible for the community.
Identifiants
pubmed: 34400477
pii: gr.275133.120
doi: 10.1101/gr.275133.120
pmc: PMC8415367
doi:
Substances chimiques
DNA Transposable Elements
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1531-1545Informations de copyright
© 2021 Playfoot et al.; Published by Cold Spring Harbor Laboratory Press.
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