The forkhead DNA-binding domain binds specific G2-rich RNA sequences.

Autor:	Zutterling C; Université Paris Cité, CNRS, Institut Jacques Monod, CNRS UMR7592, Paris 75013, France., Todeschini AL; Université Paris Cité, CNRS, Institut Jacques Monod, CNRS UMR7592, Paris 75013, France., Fourmy D; Molecular Imaging Research Center, Fontenay-aux-Roses, France.; Université Paris Saclay, France.; Institut de Biologie François Jacob, CEA, Fontenay aux Roses, France., Busso D; Université Paris Saclay, France.; Institut de Biologie François Jacob, CEA, Fontenay aux Roses, France.; CIGEx platform. UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Veaute X; Université Paris Saclay, France.; Institut de Biologie François Jacob, CEA, Fontenay aux Roses, France.; CIGEx platform. UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Ducongé F; Molecular Imaging Research Center, Fontenay-aux-Roses, France.; Université Paris Saclay, France.; Institut de Biologie François Jacob, CEA, Fontenay aux Roses, France., Veitia RA; Université Paris Cité, CNRS, Institut Jacques Monod, CNRS UMR7592, Paris 75013, France.; Université Paris Saclay, France.; Institut de Biologie François Jacob, CEA, Fontenay aux Roses, France.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2023 Dec 11; Vol. 51 (22), pp. 12367-12380.
DOI:	10.1093/nar/gkad994
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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