{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSMYD1 is a muscle‐ and heart‐enriched lysine methyltransferase that plays a central role in myogenic differentiation and cardiac development. In muscle cells, SMYD1 is robustly upregulated by miR‑206 to activate the transcription of muscle-specific genes, a process essential for myogenic differentiation and sarcomere organization. Moreover, SMYD1 methylates transcription factors such as skNAC to promote myoglobin expression, which is critical for oxygen transport in muscle tissue. In addition, studies using human embryonic stem cell–derived cardiomyocytes have shown that SMYD1 facilitates cardiac maturation and contractile force generation, while pathogenic mutations that impair its nuclear localization can disrupt cardiac gene programs and contribute to hypertrophic cardiomyopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its critical function in muscle cells, SMYD1 is expressed in vascular endothelial cells where it contributes to the regulation of angiogenesis. It enhances the DNA binding activity of the Serum Response Factor, thereby promoting endothelial cell migration and tube formation. SMYD1 levels in endothelial cells are tightly controlled by cytokine-induced pathways: inflammatory stimuli not only elevate SMYD1 expression but also trigger its SUMOylation in a promyelocytic leukemia (PML)–dependent manner, establishing a feedback loop that regulates its stability. Moreover, lipopolysaccharide-mediated stimulation upregulates SMYD1 expression, leading to increased IL‑6 secretion through NF‑κB activation and H3K4 trimethylation of the IL‑6 promoter."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSMYD1 gene transcription is also modulated by external regulators. In particular, hepatoma‑derived growth factor (HDGF) has been shown to function as a transcriptional repressor of SMYD1. HDGF interacts with the transcriptional corepressor CtBP via a non‑canonical binding motif within its PWWP domain to downregulate SMYD1 expression, an interaction further supported by studies demonstrating that modifications in the PWWP domain can impair this repressive effect."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Davide Martino Coda, Marcello Francesco Lingua, Deborah Morena, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Lysine Methyltransferase SMYD1 Regulates Myogenesis via skNAC Methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells12131695"}], "href": "https://doi.org/10.3390/cells12131695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37443729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37443729"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maggie Zi-Ying Chow, Stephanie N Sadrian, Wendy Keung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of chromatin remodeling proteins SMYD1 and SMARCD1 promotes contractile function of human pluripotent stem cell-derived ventricular cardiomyocyte in 3D-engineered cardiac tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-42953-w"}], "href": "https://doi.org/10.1038/s41598-019-42953-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31097748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31097748"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiangli Ye, Yu Qian, Qian Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SMYD1, an SRF-Interacting Partner, Is Involved in Angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0146468"}], "href": "https://doi.org/10.1371/journal.pone.0146468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26799706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26799706"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Samuel Becker, Gustav Steinemann, Weronika Karle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stability of Smyd1 in endothelial cells is controlled by PML-dependent SUMOylation upon cytokine stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20200603"}], "href": "https://doi.org/10.1042/BCJ20200603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33241844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33241844"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ahmed Shamloul, Gustav Steinemann, Kerrin Roos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Methyltransferase Smyd1 Mediates LPS-Triggered Up-Regulation of IL-6 in Endothelial Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10123515"}], "href": "https://doi.org/10.3390/cells10123515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34944023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34944023"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jun Yang, Allen D Everett "}, {"type": "b", "children": [{"type": "t", "text": "Hepatoma-derived growth factor represses SET and MYND domain containing 1 gene expression through interaction with C-terminal binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2008.12.080"}], "href": "https://doi.org/10.1016/j.jmb.2008.12.080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19162039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19162039"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jan-Kai Wu, Ying-Ying Lee, Hsin Hung, et al. 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