Functional characterization of enhancer activity during a long terminal repeat's evolution.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
25
04
2022
accepted:
23
08
2022
pubmed:
4
10
2022
medline:
5
11
2022
entrez:
3
10
2022
Statut:
ppublish
Résumé
Many transposable elements (TEs) contain transcription factor binding sites and are implicated as potential regulatory elements. However, TEs are rarely functionally tested for regulatory activity, which in turn limits our understanding of how TE regulatory activity has evolved. We systematically tested the human LTR18A subfamily for regulatory activity using massively parallel reporter assay (MPRA) and found AP-1- and CEBP-related binding motifs as drivers of enhancer activity. Functional analysis of evolutionarily reconstructed ancestral sequences revealed that LTR18A elements have generally lost regulatory activity over time through sequence changes, with the largest effects occurring owing to mutations in the AP-1 and CEBP motifs. We observed that the two motifs are conserved at higher rates than expected based on neutral evolution. Finally, we identified LTR18A elements as potential enhancers in the human genome, primarily in epithelial cells. Together, our results provide a model for the origin, evolution, and co-option of TE-derived regulatory elements.
Identifiants
pubmed: 36192170
pii: gr.276863.122
doi: 10.1101/gr.276863.122
pmc: PMC9712623
doi:
Substances chimiques
Transcription Factor AP-1
0
DNA Transposable Elements
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1840-1851Informations de copyright
© 2022 Du et al.; Published by Cold Spring Harbor Laboratory Press.
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