This family is named after the founding member lsd1 from Arabidopsis, which lacks a functional LESION SIMULATING DISEASE 1 protein (LSD1, encoded by AT4G20380). The precise molecular function of LSD1 is still under investigation, but the phenotype of lsd1 mutants is characterized by the so-called runaway cell death (RCD).   It was originally suggested that LSD1 might act as a transcription factor (TF) or scaffold protein because it possesses three zinc (Zn)-finger domains (PF06943) that could be responsible for DNA/protein binding (Dietrich et al., 1997). The Zn-finger motifs in LSD1 belong to the C2C2 class that are also present in GATA1-type transcription factors containing the conserved consensus sequence: CxxCRxxLMYxxGASxVxCxxC.  A later Y2H study revealed at least 10 potential proteins that interact with LSD1 suggesting that LSD1 may act as a scaffold protein, bringing together other cell death molecular regulators (Coll et al., 2011). These protein-protein interactions appear to be redox dependent (Czarnocka et al., 2017). To test if LSD functions as a TF, Chromatin immunoprecipitation (ChIP) was performed on 35Spro:LSD1-GFP plants that were grown in controlled laboratory (in vitro) or more variable greenhouse conditions.  Binding of LSD1 was evidenced for 15 and 13 promoters of plants grown under laboratory and greenhouse conditions, respectively (Czarnocka et al., 2017). Most of the genes whose promoters are directly or indirectly bound by LSD1 demonstrated higher expression in the lsd1 mutant and lower expression in LSD1-OE plants. The broad range of promoter sequences identified in ChIP together with the fact that LSD1 interacts with three enzymes responsible for DNA/histone methylation suggests that it may regulate gene expression by modifying the transcriptional activity of chromatin. However, further studies are needed to explain the exact role of LSD1 in transcription regulation.

A 2022 study sowed that AtLSD1 interacts with GOLDEN2-like 1 and 2 (GLK1/2) to repress their activities in Arabidopsis (Arabidopsis thaliana). Overexpression of LSD1 repressed GLK target genes, including photosynthesis-associated nuclear genes (PhANGs) indispensable for chloroplast biogenesis, whereas loss of LSD1 enhanced their expression (Li et al., 2022).

In maize there are at least 6 proteins that harbor LSD type Zn finger domains (PF06943).

Last updated June 2023 by John Gray

References:

Dietrich RA, Richberg MH, Schmidt R, Dean C, Dangl JL. A novel zinc finger protein is encoded by the Arabidopsis LSD1 gene and functions as a negative regulator of plant cell death. Cell. 1997 Mar 7;88(5):685-94. doi: 10.1016/s0092-8674(00)81911-x. PMID: 9054508.

Coll NS, Vercammen D, Smidler A, Clover C, Van Breusegem F, Dangl JL, Epple P. Arabidopsis type I metacaspases control cell death. Science. 2010 Dec 3;330(6009):1393-7. doi: 10.1126/science.1194980. Epub 2010 Nov 18. PMID: 21097903.

Czarnocka W, Van Der Kelen K, Willems P, Szechyńska-Hebda M, Shahnejat-Bushehri S, Balazadeh S, Rusaczonek A, Mueller-Roeber B, Van Breusegem F, Karpiński S. The dual role of LESION SIMULATING DISEASE 1 as a condition-dependent scaffold protein and transcription regulator. Plant Cell Environ. 2017 Nov;40(11):2644-2662. doi: 10.1111/pce.12994. Epub 2017 Jul 26. PMID: 28555890.

Li M, Lee KP, Liu T, Dogra V, Duan J, Li M, Xing W, Kim C. Antagonistic modules regulate photosynthesis-associated nuclear genes via GOLDEN2-LIKE transcription factors. Plant Physiol. 2022 Mar 28;188(4):2308-2324. doi: 10.1093/plphys/kiab600. PMID: 34951648; PMCID: PMC8968271.