Emerging role of SETD2 in the development and function of immune cells

SET domain-containing 2 (SETD2) is a methyltransferase that catalyzes trimethylation of lysine 36 on H3 (H3K36me3) in mammals, an epigenetic mark associated with actively transcribed regions. SETD2 is implicated in multiple chromatin biological processes, such as alternative splicing, transcriptiona...

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Main Authors: Longmin Chen, Yuan Zou, Yan Dong, Tian Hong, Qianqian Xu, Jing Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-11-01
Series:Genes and Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352304225001114
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author Longmin Chen
Yuan Zou
Yan Dong
Tian Hong
Qianqian Xu
Jing Zhang
author_facet Longmin Chen
Yuan Zou
Yan Dong
Tian Hong
Qianqian Xu
Jing Zhang
author_sort Longmin Chen
collection DOAJ
description SET domain-containing 2 (SETD2) is a methyltransferase that catalyzes trimethylation of lysine 36 on H3 (H3K36me3) in mammals, an epigenetic mark associated with actively transcribed regions. SETD2 is implicated in multiple chromatin biological processes, such as alternative splicing, transcriptional regulation, DNA damage repair, and maintenance of genomic integrity. Extensive studies have demonstrated that SETD2-inactivating mutations and resultant dysregulation of these functions may result in tumorigenesis. However, the role of SETD2 in the development and function of immune cells receives relatively limited attention. In this review, we seek to summarize current knowledge of the biological function and underlying mechanisms of SETD2 and highlight its important role in immune cell biology. By influencing the biological processes of immune cells, SETD2 participates in the pathogenesis of immune-related diseases, including infection, cancers, autoimmune diseases, and inflammatory diseases. Finally, we discuss challenges and prospects for targeting SETD2 in immune cells to provide guidance for treating those diseases in clinical practice.
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institution Kabale University
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publishDate 2025-11-01
publisher KeAi Communications Co., Ltd.
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series Genes and Diseases
spelling doaj-art-a2650cbdb75d4d46a8c7649bfec8916d2025-08-24T05:13:07ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610162210.1016/j.gendis.2025.101622Emerging role of SETD2 in the development and function of immune cellsLongmin Chen0Yuan Zou1Yan Dong2Tian Hong3Qianqian Xu4Jing Zhang5Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430100, China; Department of Rheumatology and Immunology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, ChinaDepartment of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, ChinaDepartment of Rheumatology and Immunology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, ChinaDepartment of Gerontology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, ChinaDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430100, ChinaDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430100, China; Corresponding author.SET domain-containing 2 (SETD2) is a methyltransferase that catalyzes trimethylation of lysine 36 on H3 (H3K36me3) in mammals, an epigenetic mark associated with actively transcribed regions. SETD2 is implicated in multiple chromatin biological processes, such as alternative splicing, transcriptional regulation, DNA damage repair, and maintenance of genomic integrity. Extensive studies have demonstrated that SETD2-inactivating mutations and resultant dysregulation of these functions may result in tumorigenesis. However, the role of SETD2 in the development and function of immune cells receives relatively limited attention. In this review, we seek to summarize current knowledge of the biological function and underlying mechanisms of SETD2 and highlight its important role in immune cell biology. By influencing the biological processes of immune cells, SETD2 participates in the pathogenesis of immune-related diseases, including infection, cancers, autoimmune diseases, and inflammatory diseases. Finally, we discuss challenges and prospects for targeting SETD2 in immune cells to provide guidance for treating those diseases in clinical practice.http://www.sciencedirect.com/science/article/pii/S2352304225001114Chromatin biological processesEpidrug discoveryH3K36me3Immune cellsSETD2
spellingShingle Longmin Chen
Yuan Zou
Yan Dong
Tian Hong
Qianqian Xu
Jing Zhang
Emerging role of SETD2 in the development and function of immune cells
Genes and Diseases
Chromatin biological processes
Epidrug discovery
H3K36me3
Immune cells
SETD2
title Emerging role of SETD2 in the development and function of immune cells
title_full Emerging role of SETD2 in the development and function of immune cells
title_fullStr Emerging role of SETD2 in the development and function of immune cells
title_full_unstemmed Emerging role of SETD2 in the development and function of immune cells
title_short Emerging role of SETD2 in the development and function of immune cells
title_sort emerging role of setd2 in the development and function of immune cells
topic Chromatin biological processes
Epidrug discovery
H3K36me3
Immune cells
SETD2
url http://www.sciencedirect.com/science/article/pii/S2352304225001114
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