The methylation of lysine residues on histone tails, a histone modification associated with gene activation and silencing, is carried out by proteins containing a conserved catalytic SET domain (PF00856, IPR001214).

It was originally identified as part of a larger conserved region present in the Drosophila Trithorax protein and was subsequently identified in the Drosophila Su(var)3-9 and 'Enhancer of zeste' proteins, from which the acronym SET is derived [Su(var)3-9, Enhancer-of-zeste and Trithorax]. The core SET domain structure contains a two-domain architecture formed by N- and Cterminal ends of the primary sequence, consisting of a conserved anti-parallel beta-barrel and a structurally variable insert that surround a unusual knot-like structure that comprises the SAM binding and enzyme active site (Jacobs et al., 2002, Marmorstein et al., 2003, Qian et al., 2006).

One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related proteins (Chen et al., 2017). Concurrent disruption of the ATX3, ATX4, and ATX5 genes caused marked reduction in H3K4me2 and H3K4me3 levels genome-wide and resulted in thousands of genes expressed ectopically. Furthermore, atx3/atx4/atx5 triple mutants resulted in exaggerated phenotypes when combined with the atx2 mutant but not with atx1. Therefore ATX3, ATX4, and ATX5 appear to be redundantly required for H3K4 di- and trimethylation at thousands of sites located across the genome (Chen et al., 2017, Ornelas-Ayala et al., 2022).

SET domain protein 725 (SDG725) is responsible for tri-methylation of histone H3 lysine 36 (H3K36me3). Knockdown of SDG725 reduced the transcripts level and H3K36me3 level of BR-related genes and resulted in erect leaves in rice (Sui et al., 2012).

There are at least 50 SET domain genes in the maize genome. A maize SET domain group protein 128 (SDG128) (GRMZM2G013794)(also known as ZmPHD41) that is closely related to Arabidopsis homologs of trithorax (ATX1). SDG128 complemented the early flowering-time phenotype of atx1, and knockdown of SDG128 using an RNAi approach resulted in a large leaf inclination. SDG128 interacts with F-box protein ZmGID2. Knockdown of ZmGID2 also resulted in a large leaf inclination. The cell dissection showed that large vascular bundles were reduced in number and the spacing of large vascular bundle increased in auricles, midrib, and sheath in knockdown transformants of SDG128 and ZmGID2. The transcripts levels and H3K4me3 levels of cell division genes, leaf-related transcriptional factor genes, and auxin biosynthesis genes were reduced in SDG128 and ZmGID2 knockdown plants. Together, these results show that SDG128 and ZmGID2 are involved in maize leaf angle development (Wang et al., 2021).

Last updated June 2023 by John Gray

References:

Marmorstein R. Structure of SET domain proteins: a new twist on histone methylation. Trends Biochem Sci. 2003 Feb;28(2):59-62. doi: 10.1016/S0968-0004(03)00007-0. PMID: 12575990.

Qian C, Zhou MM. SET domain protein lysine methyltransferases: Structure, specificity and catalysis. Cell Mol Life Sci. 2006 Dec;63(23):2755-63. doi: 10.1007/s00018-006-6274-5. PMID: 17013555.

Jacobs SA, Harp JM, Devarakonda S, Kim Y, Rastinejad F, Khorasanizadeh S. The active site of the SET domain is constructed on a knot. Nat Struct Biol. 2002 Nov;9(11):833-8. doi: 10.1038/nsb861. Erratum in: Nat Struct Biol. 2003 Jun;10(7):578. PMID: 12389038.

Chen LQ, Luo JH, Cui ZH, Xue M, Wang L, Zhang XY, Pawlowski WP, He Y. ATX3, ATX4, and ATX5 Encode Putative H3K4 Methyltransferases and Are Critical for Plant Development. Plant Physiol. 2017 Jul;174(3):1795-1806. doi: 10.1104/pp.16.01944. Epub 2017 May 26. PMID: 28550207; PMCID: PMC5490889.

Ornelas-Ayala D, Cortés-Quiñones C, Olvera-Herrera J, García-Ponce B, Garay-Arroyo A, Álvarez-Buylla ER, Sanchez MP. A Green Light to Switch on Genes: Revisiting Trithorax on Plants. Plants (Basel). 2022 Dec 23;12(1):75. doi: 10.3390/plants12010075. PMID: 36616203; PMCID: PMC9824250.

Sui P, Jin J, Ye S, Mu C, Gao J, Feng H, Shen WH, Yu Y, Dong A. H3K36 methylation is critical for brassinosteroid-regulated plant growth and development in rice. Plant J. 2012 Apr;70(2):340-7. doi: 10.1111/j.1365-313X.2011.04873.x. Epub 2012 Jan 5. PMID: 22136623.

Wang S, Zhang F, Jiang P, Zhang H, Zheng H, Chen R, Xu Z, Ikram AU, Li E, Xu Z, Fan J, Su Y, Ding Y. SDG128 is involved in maize leaf inclination. Plant J. 2021 Dec;108(6):1597-1608. doi: 10.1111/tpj.15527. Epub 2021 Oct 21. PMID: 34612535.