The forkhead DNA-binding domain binds specific G2-rich RNA sequences.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
accepted:
17
10
2023
revised:
06
09
2023
received:
31
03
2023
pubmed:
7
11
2023
medline:
7
11
2023
entrez:
7
11
2023
Statut:
ppublish
Résumé
Transcription factors contain a DNA-binding domain ensuring specific recognition of DNA target sequences. The family of forkhead (FOX) transcription factors is composed of dozens of paralogs in mammals. The forkhead domain (FHD) is a segment of about 100 amino acids that binds an A-rich DNA sequence. Using DNA and RNA PCR-SELEX, we show that recombinant FOXL2 proteins, either wild-type or carrying the oncogenic variant C134W, recognize similar DNA-binding sites. This suggests that the oncogenic variant does not alter the intrinsic sequence-specificity of FOXL2. Most importantly, we show that FOXL2 binds G2-rich RNA sequences whereas it virtually fails to bind similar sequences in DNA chemistry. Interestingly, a statistically significant subset of genes responding to the knock-down of FOXL2/Foxl2 harbor such G2-rich sequences and are involved in crucial signaling pathways and cellular processes. In addition, we show that FOXA1, FOXO3a and chimeric FOXL2 proteins containing the FHD of the former are also able to interact with some of the preferred FOXL2-binding sequences. Our results point to an unexpected and novel characteristic of the forkhead domain, the biological relevance of which remains to be explored.
Identifiants
pubmed: 37933840
pii: 7337609
doi: 10.1093/nar/gkad994
pmc: PMC10711433
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12367-12380Subventions
Organisme : University of Paris Cité
Organisme : Centre National de la Recherche Scientifique
Organisme : Agence National pour la La Recherche
Organisme : Agence Nationale pour la Recherche' Investissement d'Avenir
ID : ANR-11-INBS-0011
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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