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Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development

GATA transcription factors play crucial roles in various developmental processes in organisms ranging from flies to humans. In mammals, GATA factors are characterized by the presence of two highly conserved domains, the N-terminal (N-ZnF) and the C-terminal (C-ZnF) zinc fingers. The Drosophila GATA...

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Autores principales: Moussalem, Douaa, Augé, Benoit, Di Stefano, Luisa, Osman, Dani, Gobert, Vanessa, Haenlin, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844375/
https://www.ncbi.nlm.nih.gov/pubmed/35178397
http://dx.doi.org/10.3389/fcell.2021.795680
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author Moussalem, Douaa
Augé, Benoit
Di Stefano, Luisa
Osman, Dani
Gobert, Vanessa
Haenlin, Marc
author_facet Moussalem, Douaa
Augé, Benoit
Di Stefano, Luisa
Osman, Dani
Gobert, Vanessa
Haenlin, Marc
author_sort Moussalem, Douaa
collection PubMed
description GATA transcription factors play crucial roles in various developmental processes in organisms ranging from flies to humans. In mammals, GATA factors are characterized by the presence of two highly conserved domains, the N-terminal (N-ZnF) and the C-terminal (C-ZnF) zinc fingers. The Drosophila GATA factor Serpent (Srp) is produced in different isoforms that contains either both N-ZnF and C-ZnF (SrpNC) or only the C-ZnF (SrpC). Here, we investigated the functional roles ensured by each of these isoforms during Drosophila development. Using the CRISPR/Cas9 technique, we generated new mutant fly lines deleted for one (ΔsrpNC) or the other (ΔsrpC) encoded isoform, and a third one with a single point mutation in the N-ZnF that alters its interaction with its cofactor, the Drosophila FOG homolog U-shaped (Ush). Analysis of these mutants revealed that the Srp zinc fingers are differentially required for Srp to fulfill its functions. While SrpC is essential for embryo to adult viability, SrpNC, which is the closest conserved isoform to that of vertebrates, is not. However, to ensure its specific functions in larval hematopoiesis and fertility, Srp requires the presence of both N- and C-ZnF (SrpNC) and interaction with its cofactor Ush. Our results also reveal that in vivo the presence of N-ZnF restricts rather than extends the ability of GATA factors to regulate the repertoire of C-ZnF bound target genes.
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spelling pubmed-88443752022-02-16 Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development Moussalem, Douaa Augé, Benoit Di Stefano, Luisa Osman, Dani Gobert, Vanessa Haenlin, Marc Front Cell Dev Biol Cell and Developmental Biology GATA transcription factors play crucial roles in various developmental processes in organisms ranging from flies to humans. In mammals, GATA factors are characterized by the presence of two highly conserved domains, the N-terminal (N-ZnF) and the C-terminal (C-ZnF) zinc fingers. The Drosophila GATA factor Serpent (Srp) is produced in different isoforms that contains either both N-ZnF and C-ZnF (SrpNC) or only the C-ZnF (SrpC). Here, we investigated the functional roles ensured by each of these isoforms during Drosophila development. Using the CRISPR/Cas9 technique, we generated new mutant fly lines deleted for one (ΔsrpNC) or the other (ΔsrpC) encoded isoform, and a third one with a single point mutation in the N-ZnF that alters its interaction with its cofactor, the Drosophila FOG homolog U-shaped (Ush). Analysis of these mutants revealed that the Srp zinc fingers are differentially required for Srp to fulfill its functions. While SrpC is essential for embryo to adult viability, SrpNC, which is the closest conserved isoform to that of vertebrates, is not. However, to ensure its specific functions in larval hematopoiesis and fertility, Srp requires the presence of both N- and C-ZnF (SrpNC) and interaction with its cofactor Ush. Our results also reveal that in vivo the presence of N-ZnF restricts rather than extends the ability of GATA factors to regulate the repertoire of C-ZnF bound target genes. Frontiers Media S.A. 2022-02-01 /pmc/articles/PMC8844375/ /pubmed/35178397 http://dx.doi.org/10.3389/fcell.2021.795680 Text en Copyright © 2022 Moussalem, Augé, Di Stefano, Osman, Gobert and Haenlin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Moussalem, Douaa
Augé, Benoit
Di Stefano, Luisa
Osman, Dani
Gobert, Vanessa
Haenlin, Marc
Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title_full Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title_fullStr Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title_full_unstemmed Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title_short Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development
title_sort two isoforms of serpent containing either one or two gata zinc fingers provide functional diversity during drosophila development
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844375/
https://www.ncbi.nlm.nih.gov/pubmed/35178397
http://dx.doi.org/10.3389/fcell.2021.795680
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