ZF-HD proteins are a subfamily of Homeodomain proteins, consisting of 14 members in Arabidopsis. Most of these proteins do not contain an intrinsic activation domain, suggesting that interactions with other factors are required for transcriptional activation. In Arabidopsis, the family members are all expressed predominantly or exclusively in floral tissue, suggesting a regulatory role in floral development (Tan and Irish, 2006).

The homeodomain (HD) is a 60-amino acid DNA-binding domain (BD) found in many transcription factors. HD-containing proteins are found in diverse organisms such as humans, Drosophila, nematode worms, and plants, where they play important roles in development. The crystal structures of different HDs bound to DNA have been isolated and the structures have been found to be remarkably similar. The HD consists of three α helices and a flexible N-terminal arm. Helix III, the recognition helix, packs against the DNA major groove and makes specific contacts with the DNA. HD proteins have been explicitly shown to act as transcription factors because they bind to promoter sequences and act to modulate mRNA synthesis.

Class I knox genes appear to play similar roles in controlling the balance between meristematic and determinate growth during plant development. Class I knox genes are typically expressed in the shoot apical meristem and the developing stem, but not in determinate lateral organs such as floral organs and leaves (Hake et al., 2004).  The WUSCHEL-related homeobox (WOX) class of HD-containing genes appears to be essential for embryonic patterning, specifying different regions in the embryo (Breuninger et al., 2008). Class III HD-Leu zipper (ZIP) proteins are characterized by a START domain and a HD-ZIP at the N terminus. The five Class III HD-ZIP members in Arabidopsis all appear to be regulated by mRNAs. Three members of this family of genes, PHAVOLUTA, PHABULOSA, and REVOLUTA, are involved in determining adaxial identity in leaves and embryos (Du et al., 2018). The HDs of the ZF-HD proteins share some similarities with other known HDs in Arabidopsis, but they contain distinct features that cluster them as a unique class of plant HD-containing proteins (Tan and Irish, 2006).  Yeast (Saccharomyces cerevisiae) two-hybrid matrix analyses of the Arabidopsis ZF-HD proteins reveal that these proteins both homo- and heterodimerize, which may contribute to greater selectivity in DNA binding. These assays also revealed that most of these proteins do not contain an intrinsic activation domain, suggesting that interactions with other factors are required for transcriptional activation (Tan and Irish, 2006). This subset of HD TFs appear to play overlapping regulatory roles in floral development and may involve an interplay with GRF TFs  (Tan and Irish, 2006, Ferela et al, 2023).

At least 21 ZHD genes have been identified in the maize genome. Through sequence alignment and phylogenetic analysis, these ZHD proteins have been divided into eight groups that have variations in gene structure, motif distribution, and a conserved ZF domain (Islam et al., 2022). A preliminary study suggests that ZmZHD9-overexpressing plants showed increased tolerance to drought stress compared with wild-type plants, evaluated by higher RWC and proline content, higher SOD and POD activity, lower REL and MDA content in transgenic plants under drought stress (Zhang et al., 2020).

Last updated June 2023 by John Gray

References:

Tan QK, Irish VF. The Arabidopsis zinc finger-homeodomain genes encode proteins with unique biochemical properties that are coordinately expressed during floral development. Plant Physiol. 2006 Mar;140(3):1095-108. doi: 10.1104/pp.105.070565. Epub 2006 Jan 20. PMID: 16428600; PMCID: PMC1400567.

Islam MAU, Nupur JA, Khalid MHB, Din AMU, Shafiq M, Alshegaihi RM, Ali Q, Ali Q, Kamran Z, Manzoor M, Haider MS, Shahid MA, Manghwar H. Genome-Wide Identification and In Silico Analysis of ZF-HD Transcription Factor Genes in Zea mays L. Genes (Basel). 2022 Nov 14;13(11):2112. doi: 10.3390/genes13112112. PMID: 36421787; PMCID: PMC9690586.

Hake S, Smith HM, Holtan H, Magnani E, Mele G, Ramirez J. The role of knox genes in plant development. Annu Rev Cell Dev Biol. 2004;20:125-51. doi: 10.1146/annurev.cellbio.20.031803.093824. PMID: 15473837.

Du F, Guan C, Jiao Y. Molecular Mechanisms of Leaf Morphogenesis. Mol Plant. 2018 Sep 10;11(9):1117-1134. doi: 10.1016/j.molp.2018.06.006. Epub 2018 Jun 28. PMID: 29960106.

Breuninger H, Rikirsch E, Hermann M, Ueda M, Laux T. Differential expression of WOX genes mediates apical-basal axis formation in the Arabidopsis embryo. Dev Cell. 2008 Jun;14(6):867-76. doi: 10.1016/j.devcel.2008.03.008. PMID: 18539115.

Ferela A, Debernardi JM, Rosatti S, Liebsch D, Schommer C, Palatnik JF. Interplay among ZF-HD and GRF transcription factors during Arabidopsis leaf development. Plant Physiol. 2023 Mar 17;191(3):1789-1802. doi: 10.1093/plphys/kiad009. PMID: 36652435; PMCID: PMC10022616.

Zhang, P., Wei, L., Cao, L., Qiu, X., Fu, J., Wang, G., ... & Wang, T. (2020). Function analysis of ZmZHD9, a positive regulator in drought stress response in transgenic maize. https://doi.org/10.21203/rs.3.rs-119004/v1