Table 1.
Studies on SMYD proteins and the main findings related to immunology.
| SMYD | Model | Main findings | References |
|---|---|---|---|
| SMYD1 | pGL-2 and pGL-IO cell lines | SMYD1 expression in cytotoxic T lymphocytes | (Hwang and Gottlieb 1997) |
| SMYD1 | Muscle-specific Smyd1 KO mice, N = 3 | Downregulation of Il-6, TNFα, Ccl6, Ccl7, Ccl9, Foxp3, Bcl11A, RunX1 and Cbfβ in brown adipose tissue | (Rasmussen and Tucker 2018) |
| SMYD1 | Yak, N = 48 | Copy number variations in SMYD1 | (Wang et al., 2019) |
| SMYD1 | AnWj- negative humans, N = 6 | R320Q substitution in SMYD1 | (Yahalom et al., 2018) |
| SMYD1 | Patients with velocardiofacial syndrome, N = 88 | Identification of SMYD1 as a putative pathogenic gene | (Wu et al., 2019) |
| SMYD1 | Patients with splenic marginal zone lymphoma, N = 26 | Recurrent mutations in SMYD1 | (Peveling-Oberhag et al., 2015) |
| SMYD2 | Monkey Cos7L cell line | SMYD2 methylation of GFI1 provokes recruitment of LSD1 and repression of the transcription of GFI1 target genes, leading to normal and/or malignant haematopoiesis | (Velinder et al., 2016) |
| SMYD2 | C57BL/6 mice, N = 3 | Upregulation of Smyd2 abrogates macrophage production of IL-6 and TNFα by catalysing H3K36 dimethylation of Tnf and Il6 promoters and suppression of NFκB and ERK signalling | (Xu et al., 2015) |
| SMYD2 | CD-1 female mice, N = 6-10 | SMYD2 catalyses H3K36 dimethylation and inhibits IL-6 and TNFα expression after bisphenol A and phthalate exposure of peritoneal macrophages | (Li et al., 2018) |
| SMYD2 | Human monocyte THP-1 cell line and human primary monocytes | The TNFα inhibitor etanercept acts by suppressing LPS-induced CCL2 expression by decreasing protein levels of SMYD2 and H3K36me3 in the CCL2 promoter region | (Lin et al., 2017) |
| SMYD2 | Patients with leukaemia, N = 50 Haematopoietic stem cell-specific SMYD2 KO mice, N = 3-8 |
SMYD2 overexpression in many types of leukaemia Positive correlation between high SMYD2 and low overall patient survival in B-cell acute lymphoblastic leukaemia Aberrant haematopoiesis in haematopoietic stem cell-specific SMYD2 KO mice |
(Brown et al., 2020) |
| SMYD2 | Patients with leukaemia, N = 83 |
SMYD2 overexpression in acute lymphoblastic leukaemia Positive correlation between high SMYD2 and low overall patient survival in acute lymphoblastic leukaemia Decrease in SMYD2 expression 29 days after chemotherapy related to treatment response |
(Sakamoto et al., 2014) |
| SMYD2 | Patients with leukaemia, N = 134 |
SMYD2 overexpression in B lineage acute lymphoblastic leukaemia, associated with bad prognosis Reduction of SMYD2 expression levels after remission |
(Zhang et al., 2020) |
| SMYD2 | SMYD2 KO mice, N = 12 | Normal haematopoiesis in SMYD2 KO mice Reduced penetrance of death due to MLL-AF9/NRasG12D-induced acute myeloid leukaemia in SMYD2 KO mice Competitive disadvantages of SMYD2 KO acute myeloid leukaemia cells |
(Bagislar et al., 2016) |
| SMYD2 | Patients with leukaemia, N = 59 |
SMYD2 and SMYD3 upregulation chronic lymphocytic leukaemia Residual expression of SMYD2 and SMYD3 correlated with elevated white blood cells count and a complex karyotype |
(Oliveira-Santos et al., 2016). |
| SMYD2 | RUNX2/MYC transgenic mice, N = 3 | Smyd2 overexpression in premalignant thymus from RUNX2/MYC transgenic mice | (Hay et al., 2019) |
| SMYD2 | Patients with leukaemia and hematopoietic TEX cell line | Low expression of SMYD2 in acute myeloid leukaemia negatively correlates with treatment response and probability of tumour-free survival SMYD2 KO human acute myeloid leukaemia cells are more resistant to DNA damage caused by irradiation due to transient quiescence |
(Zipin-Roitman et al., 2017) |
| SMYD2 | Female BALB/c mice, N = 3 Murine J774 macrophage cell line |
Smyd2 upregulation and H3K36 dimethylation at TNFα promoter after infection with Leishmania donovani SMYD2 inhibition protects against Leishmania donovani infection |
(Parmar et al. 2020) |
| SMYD2 | CD4+ T cells from patients infected HIV-1, HEK293T and J-Lat cell lines | SMYD2 mediates H4K20 monomethylation in the HIV-1 promoter located in the 5’ long terminal repeat. H4K20me1 promotes association of L3MBTL1 with the 5′ long terminal repeat SYMD2 inhibition reactivated HIV-1 |
(Boehm et al., 2017) |
| SMYD3 | Human primary monocytes | Decreased SMYD3 mRNA and cell proliferation 18 h after IFNγ treatment of CSF1 differentiated primary human macrophages | (Yildirim-Buharalioğlu et al., 2017) |
| SMYD3 | Patients with diabetes (T1DM and T2DM), N = 19-21 | Under hyperglycaemic conditions, SMYD3 activates S100A12 expression by methylation of S100A12 promoter in M1 macrophages | (Mossel et al., 2020) |
| SMYD3 | Many cell lines | SMYD3 in T cell lines and primary T cells directly interacts with HTLV-1 Tax and supports Tax cytoplasmic localisation | (Yamamoto et al., 2011) |
| SMYD3 | Female C57BL/6 mice, N = 3 | SMYD3 catalyses H3K4me3 in the promoter region of the foxp3 gene and regulates its expression in iTreg cells Inhibition of SMYD3 impairs iTreg cell formation. SMYD3 KO mice infected with respiratory syncytial virus display exaggerated inflammatory responses and aggravation of the disease |
(Nagata et al., 2015) |
| SMYD3 | Human Hodgkin lymphoma L1236 and L428 cell lines | SMYD3 participates in Hodgkin lymphoma development via H3K4 methylation at the promoter of 15-LOX-1 | (Liu et al., 2012) |
| SMYD3 | Human chronic lymphocytic leukaemia MEC1 cell line Patients with leukaemia, N = 20 Many human chronic lymphocytic leukaemia cell lines |
SMYD3 upregulation by STAT3 in chronic lymphocytic leukaemia The STAT3-SMYD3 axis promotes carcinogenesis, since high SMYD3 levels showed a negative correlation with suppression of cell proliferation and invasion capacity Downregulation of the phosphorylation of STAT3 suppresses STAT3 binding to the SMYD3 promoter and SMYD3 expression |
(Ma et al., 2019; Lin et al., 2019) |
| SMYD3 | Human leukaemia K562 and HL- 60 cell lines | Overexpression of SMYD3 in a leukaemia cell line induces c-Met expression | (Zou et al., 2009) |
| SMYD3 | Patients with human papilloma virus-negative squamous cell carcinoma of the head and neck, N = 364, and derived cell lines | Inhibition of SMYD3 causes CXCL9, CXCL10, CXCL11 and TAP1 upregulation in human papilloma virus -negative squamous cell carcinoma of the head and neck cell lines | (Vougiouklakis et al., 2017) |
| SMYD3 | Human multiple myeloma U266 cell line | Triptolide downregulates SMYD3 in a human multiple myeloma cell line | (Zhao et al., 2010) |
| SMYD3 | Human multiple myeloma U266 cell line | Berberine downregulates SMYD3 in a human multiple myeloma cell line | (Wang et al., 2016) |
| SMYD4 | Patients with rheumatoid arthritis | SMYD4 overexpression in TNFα-stimulated synovial fibroblasts from patients with rheumatoid arthritis | (Araki et al., 2018) |
| SMYD5 | Primary murine macrophages and many cell lines | SMYD5 basal repression of TLR4-responsive promoters in macrophages by catalysing H4K20me3 | (Stender et al., 2012) |
N indicates the number of subjects per experimental group. Abbreviations: KO; knockout, Il-6; interleukin-6, TNFα; tumour necrosis factor-alpha, Ccl6; chemokine (C–C motif) ligand 6, Ccl7; chemokine (C–C motif) ligand 7, Ccl9; chemokine (C–C motif) ligand 9, Foxp3; forkhead box P3, Bcl11A; BAF chromatin remodelling complex subunit BCL11A, RunX1; RUNX family transcription factor 1, Cbfβ; core binding factor β, GFI1; growth factor independent 1 transcription repressor, LSD1; lysine demethylase 1A, H3K36me2; histone 3 lysine 36 dimethylation, NFκB; nuclear factor kappa B subunit 1, ERK; extracellular signal-regulated kinase, LPS; lipopolysaccharide, CCL2; C–C motif chemokine ligand 2, H3K36me3; histone 3 lysine 36 trimethylation, RunX2; RUNX family transcription factor 2, Myc; myelocytomatosis oncogene, HIV-1; immunodeficiency virus type 1, H4K20me1; histone 4 lysine 20 monomethylation, L3MBTL1; L3MBTL histone methyl-lysine binding protein 1, IFNγ; interferon gamma, CSF1; colony-stimulating factor 1, T1DM; type 1 diabetes, T2DM; type 2 diabetes, S100A12; S100 calcium binding protein A12, HTLV-1; human T-cell lymphotropic virus type 1/human T-cell leukaemia type 1, H3K4me3; histone 3 lysine 4 trimethylation, iTreg; inducible regulatory T cells, H3K4me; histone 3 lysine 4 methylation, 15-LOX-1; 15-Lipoxygenase-1, STAT3; signal transducer and activator of transcription 3, Cxcl9; C-X-C motif chemokine ligand 9, Cxcl10; C-X-C motif chemokine ligand 10, Cxcl11; C-X-C motif chemokine ligand 11, Tap1; transporter 1, ATP binding cassette subfamily B member, TLR4; Toll-like receptor 4, H4K20me3; histone 4 lysine 20 trimethylation.