Does ferredoxin I (Azotobacter
) represent a novel class of DNA-binding proteins that regulate gene expression in response to cellular iron(II)?

Abstract MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate their activities and the precise mechanisms of this coordination are not well understood. RBPs often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa-1 and asd-2, genetically interacted with all of the miRNA mutants tested, whereas other KH domain genes showed genetic interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

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The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation

Quarterly Reviews of Biophysics ◽

10.1017/s0033583510000089 ◽

2010 ◽

Vol 43 (1) ◽

pp. 1-21 ◽

Cited By ~ 140

Author(s):

Aaron Klug

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Zinc Finger ◽

Binding Proteins ◽

Zinc Fingers ◽

Dna Binding Proteins ◽

Functional Domains ◽

Control Of Gene Expression ◽

Activation Domains ◽

Finger Peptides

AbstractA long-standing goal of molecular biologists has been to construct DNA-binding proteins for the control of gene expression. The classical Cys2His2 (C2H2) zinc finger design is ideally suited for such purposes. Discriminating between closely related DNA sequences both in vitro and in vivo, this naturally occurring design was adopted for engineering zinc finger proteins (ZFPs) to target genes specifically.Zinc fingers were discovered in 1985, arising from the interpretation of our biochemical studies on the interaction of the Xenopus protein transcription factor IIIA (TFIIIA) with 5S RNA. Subsequent structural studies revealed its three-dimensional structure and its interaction with DNA. Each finger constitutes a self-contained domain stabilized by a zinc (Zn) ion ligated to a pair of cysteines and a pair of histidines and also by an inner structural hydrophobic core. This discovery showed not only a new protein fold but also a novel principle of DNA recognition. Whereas other DNA-binding proteins generally make use of the 2-fold symmetry of the double helix, functioning as homo- or heterodimers, zinc fingers can be linked linearly in tandem to recognize nucleic acid sequences of varying lengths. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA (or RNA). It is therefore not surprising that the zinc finger is found widespread in nature, including 3% of the genes of the human genome.The zinc finger design can be used to construct DNA-binding proteins for specific intervention in gene expression. By fusing selected zinc finger peptides to repression or activation domains, genes can be selectively switched off or on by targeting the peptide to the desired gene target. It was also suggested that by combining an appropriate zinc finger peptide with other effector or functional domains, e.g. from nucleases or integrases to form chimaeric proteins, genomes could be modified or manipulated.The first example of the power of the method was published in 1994 when a three-finger protein was constructed to block the expression of a human oncogene transformed into a mouse cell line. The same paper also described how a reporter gene was activated by targeting an inserted 9-base pair (bp) sequence, which acts as the promoter. Thus, by fusing zinc finger peptides to repression or activation domains, genes can be selectively switched off or on. It was also suggested that, by combining zinc fingers with other effector or functional domains, e.g. from nucleases or integrases, to form chimaeric proteins, genomes could be manipulated or modified.Several applications of such engineered ZFPs are described here, including some of therapeutic importance, and also their adaptation for breeding improved crop plants.

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Integrating sequence and gene expression information predicts genome-wide DNA-binding proteins and suggests a cooperative mechanism

Nucleic Acids Research ◽

10.1093/nar/gkx1166 ◽

2017 ◽

Vol 46 (1) ◽

pp. 54-70 ◽

Cited By ~ 3

Author(s):

Shandar Ahmad ◽

Philip Prathipati ◽

Lokesh P Tripathi ◽

Yi-An Chen ◽

Ajay Arya ◽

...

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Binding Proteins ◽

Dna Binding Proteins ◽

Gene Expression Information ◽

Genome Wide

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Modulation of Gene Expression Through DNA-Binding Proteins: Is There a Regulatory Code?

Modern Trends in Human Leukemia VI New Results in Clinical and Biological Research Including Pediatric Oncology - Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ◽

10.1007/978-3-642-70385-0_49 ◽

1985 ◽

pp. 217-223 ◽

Cited By ~ 2

Author(s):

M. Beato

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Binding Proteins ◽

Dna Binding Proteins ◽

Modulation Of Gene Expression

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Genetic and epigenetic control of the spatial organization of the genome

Molecular Biology of the Cell ◽

10.1091/mbc.e16-03-0149 ◽

2017 ◽

Vol 28 (3) ◽

pp. 364-369 ◽

Cited By ~ 9

Author(s):

Jason Brickner

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Chromatin Structure ◽

Binding Sites ◽

Spatial Organization ◽

Binding Proteins ◽

Dna Binding Proteins ◽

Adaptive Function ◽

Nuclear Structures ◽

Eukaryotic Genomes

Eukaryotic genomes are spatially organized within the nucleus by chromosome folding, interchromosomal contacts, and interaction with nuclear structures. This spatial organization is observed in diverse organisms and both reflects and contributes to gene expression and differentiation. This leads to the notion that the arrangement of the genome within the nucleus has been shaped and conserved through evolutionary processes and likely plays an adaptive function. Both DNA-binding proteins and changes in chromatin structure influence the positioning of genes and larger domains within the nucleus. This suggests that the spatial organization of the genome can be genetically encoded by binding sites for DNA-binding proteins and can also involve changes in chromatin structure, potentially through nongenetic mechanisms. Here I briefly discuss the results that support these ideas and their implications for how genomes encode spatial organization.

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