{"title":"The Role of Histone Methyltransferase SETDB1 in Normal and Malignant Hematopoiesis.","authors":"Yu-Hsuan Chang, Susumu Goyama","doi":"10.1111/cas.70116","DOIUrl":null,"url":null,"abstract":"<p><p>SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase, functioning in transcriptional silencing of the transposable elements (TEs), endogenous retroviruses (ERVs), interferon-stimulated genes (ISGs), and immune cell-related molecules. SETDB1 collaborates with cofactors such as ATF7IP and TRIM28 and functions in concert with DNA methylation to maintain gene repression in both stem cells and differentiated somatic cells. Given its gene targets, recent studies have shown that SETDB1 is a critical immune checkpoint gene in both solid and hematological tumors. In this review, we first discuss the role of SETDB1 in gene regulation through its histone methyltransferase activity, including an overview of its structural features and key cofactors. We then highlight the lineage-specific roles of SETDB1 in both normal hematopoietic processes and hematological malignancies, emphasizing its function as an immune checkpoint molecule that suppresses natural killer (NK) cell-mediated antileukemia responses.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cas.70116","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase, functioning in transcriptional silencing of the transposable elements (TEs), endogenous retroviruses (ERVs), interferon-stimulated genes (ISGs), and immune cell-related molecules. SETDB1 collaborates with cofactors such as ATF7IP and TRIM28 and functions in concert with DNA methylation to maintain gene repression in both stem cells and differentiated somatic cells. Given its gene targets, recent studies have shown that SETDB1 is a critical immune checkpoint gene in both solid and hematological tumors. In this review, we first discuss the role of SETDB1 in gene regulation through its histone methyltransferase activity, including an overview of its structural features and key cofactors. We then highlight the lineage-specific roles of SETDB1 in both normal hematopoietic processes and hematological malignancies, emphasizing its function as an immune checkpoint molecule that suppresses natural killer (NK) cell-mediated antileukemia responses.
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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