The C2H2 zinc-finger domain (PF00096) is the classical zinc finger domain that was first defined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (Xenopus laevis) transcription factor IIIA (Hanas et al., 1983) and soon after in the Krüppel transcription factor from Drosophila (Klug 2010).  It is now recognized to be present in many proteins (~ 3% of the human genome) and there are a number of types of zinc fingers, each with a unique three-dimensional architecture. Most zinc finger containing proteins (ZFPs) function as interaction modules that bind DNA, RNA, proteins, or other small, useful molecules.  In general, zinc fingers coordinate zinc ions with a combination of cysteine and histidine residues. Originally, the number and order of these residues was used to classify different types of zinc fingers ( e.g., Cys2His2, Cys4, and Cys6). More recently, a more systematic method has been used to classify zinc finger proteins instead. This method classifies zinc finger proteins into "fold groups" based on the overall shape of the protein backbone in the folded domain. The most common "fold groups" of zinc fingers are the Cys2His2-like (the "classic zinc finger"), treble clef, and zinc ribbon.  The C2H2 zinc finger is common in transcription factors. Such domains adopt a simple ββα fold and have the amino acid sequence motif X2-Cys-X2,4-Cys-X12-His-X3,4,5-His (Pabo et al., 2001).  The amino terminal part of the helix binds the major groove in DNA binding zinc fingers.

In plants C2H2 zinc-finger proteins play important roles in plant development including floral organogenesis leaf initiation lateral shoot initiation gametogenesis and seed development. In Arabidopsis, AtZFP1 is thought to play a role in shoot development, downstream of photomorphogenic activation (Chrispeels et al., 2000). AtZFP1 expression is induced about three days after germination, before the expansion of the true leaves. Dark-grown plants, in which photomorphogenesis is repressed, have no detectable AtZFP1 expression in the shoot apex.  Another C2H2 TF AtZFP3 is involved in salt and osmotic stress response. Constitutive expression of ZFP3 enhanced tolerance of plants to salt and osmotic stress while the zfp3 mutant plants displays reduced tolerance (Zhang et al., 2015).

A genome-wide study identified 150 C2H2 members in maize (Li et al., 2023). These encode predicted proteins varying in molecular weight  from 135.1 kDa to 10.1 kDa.  An analysis of promoter cis elements showed that the ZmC2H2 genes contain many light-response elements, plant hormone-response elements, and stress-response elements. An analysis of the transcriptome data showed that most of the ZmC2H2 genes responded to cold stress (Li et al., 2023).  A real-time quantitative PCR (qRT-PCR) analysis showed that ZmC2H2-69, ZmC2H2-130, and ZmC2H2-76 were significantly upregulated, and that ZmC2H2-149, ZmC2H2-33, and ZmC2H2-38 were significantly downregulated in cold tolerant versus cold sensitive maize lines. 

Last updated June 2023 by John Gray

References:

Hanas JS, Hazuda DJ, Bogenhagen DF, Wu FY, Wu CW. Xenopus transcription factor A requires zinc for binding to the 5 S RNA gene. J Biol Chem. 1983 Dec 10;258(23):14120-5. PMID: 6196359.

Klug A. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem. 2010;79:213-31. doi: 10.1146/annurev-biochem-010909-095056. PMID: 20192761.

Pabo CO, Peisach E, Grant RA. Design and selection of novel Cys2His2 zinc finger proteins. Annu Rev Biochem. 2001;70:313-40. doi: 10.1146/annurev.biochem.70.1.313. PMID: 11395410.

Li S, Li Y, Cai Q, Li X, Sun Y, Yu T, Yang J, Zhang J. Analysis of the C2H2 Gene Family in Maize (Zea mays L.) under Cold Stress: Identification and Expression. Life (Basel). 2022 Dec 31;13(1):122. doi: 10.3390/life13010122. PMID: 36676071; PMCID: PMC9863836.

Chrispeels HE, Oettinger H, Janvier N, Tague BW. AtZFP1, encoding Arabidopsis thaliana C2H2 zinc-finger protein 1, is expressed downstream of photomorphogenic activation. Plant Mol Biol. 2000 Jan;42(2):279-90. doi: 10.1023/a:1006352809700. PMID: 10794528.

Zhang A, Liu D, Hua C, Yan A, Liu B, Wu M, Liu Y, Huang L, Ali I, Gan Y. The Arabidopsis Gene zinc finger protein 3(ZFP3) Is Involved in Salt Stress and Osmotic Stress Response. PLoS One. 2016 Dec 15;11(12):e0168367. doi: 10.1371/journal.pone.0168367. PMID: 27977750; PMCID: PMC5158053.