Abstract
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.
Highlights
GATA factors are DNA binding proteins that were named after the consensus nucleic acid sequence they recognize
SrpC transcript is obtained by the substitution of the N-ZnF coding exon 4A by the alternative exon 4B that encodes a protein region lacking any known motif. This alternative splicing mechanism leading to the production of the SrpC protein isoform is thought to have arisen in a second evolutionary step, through a specific exon duplication subjected to mutually exclusive splicing (Yue et al, 2016)
We investigate the role of two srp isoforms during Drosophila development
Summary
GATA factors are DNA binding proteins that were named after the consensus nucleic acid sequence they recognize. Metazoan GATA genes evolved from two ancestral genes, GATA123 and GATA456 (Gillis et al, 2008; Gillis et al, 2009), and expanded either by two genome duplications in vertebrates, which have six paralogs, or by a specific duplication of GATA456 paralogs, as in the fruit fly Drosophila melanogaster that has five GATA genes (Gillis et al, 2008; Gillis et al, 2009) They play essential roles in many developmental processes by regulating cell proliferation, cellfate specification and differentiation. Mutations affecting the GATA4, GATA5 and GATA6 factors that are expressed during the mammalian heart development, are associated to cardiac diseases (Whitcomb et al, 2020)
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