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The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.

ABSTRACT: The Cys2His2 zinc finger is the most common DNA-binding domain expanding in metazoans since the fungi human split. A proposed catalyst for this expansion is an arms race to silence transposable elements yet it remains poorly understood how this domain is able to evolve the required specificities. Likewise, models of its DNA binding specificity remain error prone due to a lack of understanding of how adjacent fingers influence each other's binding specificity. Here, we use a synthetic approach to exhaustively investigate binding geometry, one of the dominant influences on adjacent finger function. By screening over 28 billion protein-DNA interactions in various geometric contexts we find the plasticity of the most common natural geometry enables more functional amino acid combinations across all targets. Further, residues that define this geometry are enriched in genomes where zinc fingers are prevalent and specificity transitions would be limited in alternative geometries. Finally, these results demonstrate an exhaustive synthetic screen can produce an accurate model of domain function while providing mechanistic insight that may have assisted in the domains expansion.

SUBMITTER: Mueller AL

PROVIDER: S-EPMC7293014 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.

Mueller April L AL Corbi-Verge Carles C Giganti David O DO Ichikawa David M DM Spencer Jeffrey M JM MacRae Mark M Garton Michael M Kim Philip M PM Noyes Marcus B MB

Nucleic acids research 20200601 11

The Cys2His2 zinc finger is the most common DNA-binding domain expanding in metazoans since the fungi human split. A proposed catalyst for this expansion is an arms race to silence transposable elements yet it remains poorly understood how this domain is able to evolve the required specificities. Likewise, models of its DNA binding specificity remain error prone due to a lack of understanding of how adjacent fingers influence each other's binding specificity. Here, we use a synthetic approach to ...[more]

PMID: 32383734

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Project description:Abscisic acid (ABA) is one of the five classical phytohormones involved in increasing the tolerance of plants for various kinds of stresses caused by abiotic or biotic factors, and it also plays important roles in regulating the activation of innate immune cells and glucose homeostasis in mammals. For these reasons, as a "stress hormone," ABA has recently received attention as a candidate drug for agriculture and biomedical applications, prompting significant development of ABA synthesis. Some plant-pathogenic fungi can synthesize natural ABA. The fungus Botrytis cinerea has been used for biotechnological production of ABA. Identification of the transcription factors (TFs) involved in regulation of ABA biosynthesis in B. cinerea would provide new clues to understand how ABA is synthesized and regulated. In this study, we defined a novel Cys2His2 TF, BcabaR1, that regulates the transcriptional levels of ABA synthase genes (bcaba1, bcaba2, bcaba3, and bcaba4) in an ABA-overproducing mutant, B. cinerea TBC-A. Electrophoretic mobility shift assays revealed that recombinant BcabaR1 can bind specifically to both a 14-nucleotide sequence motif and a 39-nucleotide sequence motif in the promoter region of bcaba1 to -4 genes in vitro A decreased transcriptional level of the bcabaR1 gene in B. cinerea led to significantly decreased ABA production and downregulated transcription of bcaba1 to -4 When bcabaR1 was overexpressed in B. cinerea, ABA production was significantly increased, with upregulated transcription of bcaba1 to -4 Thus, in this study, we found that BcabaR1 acts as a positive regulator of ABA biosynthesis in B. cinereaIMPORTANCE Abscisic acid (ABA) could make a potentially important contribution to theoretical research and applications in agriculture and medicine. Botrytis cinerea is a plant-pathogenic fungus that was found to produce ABA. There has been a view that ABA is related to the interaction between pathogenic fungi and plants. Identification of regulatory genes involved in ABA biosynthesis may facilitate an understanding of the underlying molecular mechanisms of ABA biosynthesis and the pathogenesis of B. cinerea Here, we present a positive regulator, BcabaR1, of ABA biosynthesis in B. cinerea that can affect the transcriptional level of the ABA biosynthesis gene cluster, bcaba1 to -4, by directly binding to the conserved sequence elements in the promoter of the bcaba1 to -4 genes. This TF was found to be specifically involved in regulation of ABA biosynthesis. This work provides new clues for finding other ABA biosynthesis genes and improving ABA yield in B. cinerea.

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The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.

Publications

The geometric influence on the Cys2His2 zinc finger domain and functional plasticity.

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