Roles of SETD2 in Leukemia-Transcription, DNA-Damage, and Beyond

International Journal of Molecular Sciences
Anna SkuchaFlorian Grebien

Abstract

The non-redundant histone methyltransferase SETD2 (SET domain containing 2; KMT3A) is responsible for tri-methylation of lysine 36 on histone H3 (H3K36me3). Presence of the H3K36me3 histone mark across the genome has been correlated with transcriptional activation and elongation, but also with the regulation of DNA mismatch repair, homologous recombination and alternative splicing. The role of SETD2 and the H3K36me3 histone mark in cancer is controversial. SETD2 is lost or mutated in various cancers, supporting a tumor suppressive role of the protein. Alterations in the SETD2 gene are also present in leukemia patients, where they are associated with aggressive disease and relapse. In line, heterozygous SETD2 loss caused chemotherapy resistance in leukemia cell lines and mouse models. In contrast, other studies indicate that SETD2 is critically required for the proliferation of leukemia cells. Thus, although studies of SETD2-dependent processes in cancer have contributed to a better understanding of the SETD2⁻H3K36me3 axis, many open questions remain regarding its specific role in leukemia. Here, we review the current literature about critical functions of SETD2 in the context of hematopoietic malignancies.

References

Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·M MaoZ Chen
Aug 13, 1998·Human Molecular Genetics·P W FaberM E MacDonald
Feb 13, 2002·Molecular and Cellular Biology·Brian D StrahlC David Allis
Apr 29, 2004·Nature Structural & Molecular Biology·Steven Hahn
Nov 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ming LiPei Zhou
Dec 1, 2006·Nucleic Acids Research·Peng ZhangJianping Ding
Sep 17, 2008·Molecular and Cellular Biology·Mukta UllahXiang-Jiao Yang
Feb 3, 2009·Nature Genetics·Paulina Kolasinska-ZwierzJulie Ahringer
Feb 6, 2010·Science·Reini F LucoTom Misteli
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ming HuZhu Chen
Apr 20, 2010·Nature Structural & Molecular Biology·Alessandro VezzoliMark Bycroft
Jul 12, 2011·Cancer Cell·Kathrin M BerntScott A Armstrong
Jul 28, 2011·Nature Structural & Molecular Biology·Sérgio Fernandes de AlmeidaMaria Carmo-Fonseca
Jan 13, 2012·Nature·Jinghui ZhangCharles G Mullighan
Jan 24, 2012·Nature Reviews. Molecular Cell Biology·Eric J Wagner, Phillip B Carpenter
Jul 10, 2012·Nature Structural & Molecular Biology·Mads DaugaardMarja Jäättelä
Oct 10, 2012·Journal of the American Chemical Society·Weihong ZhengMinkui Luo
Nov 13, 2012·Nature Structural & Molecular Biology·Catherine A MusselmanTatiana G Kutateladze
Dec 6, 2012·Nature Structural & Molecular Biology·Catherine A MusselmanTatiana G Kutateladze
Jan 18, 2013·Nucleic Acids Research·Sílvia CarvalhoSérgio Fernandes de Almeida
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jan 28, 2014·Nucleic Acids Research·Hiroshi OkudaAkihiko Yokoyama
May 12, 2015·Nature Biotechnology·Junwei ShiChristopher R Vakoc
Nov 26, 2015·Cancer Cell·Sophia X PfisterTimothy C Humphrey
May 8, 2016·Cancer Discovery·Li ZhuMichael L Cleary
Aug 16, 2016·Cell·In Young ParkCheryl Lyn Walker

❮ Previous
Next ❯

Citations

Oct 31, 2019·Journal of Clinical Pathology·Huan Ying ChangPuay Hoon Tan
Feb 6, 2020·Cell & Bioscience·Zhongxing SunDong Fang
Aug 30, 2020·Journal of Experimental & Clinical Cancer Research : CR·Cheng YangLihui Wang
Aug 14, 2019·Journal of Cellular Biochemistry·Chunling LiLing Gu
Nov 5, 2019·Frontiers in Cell and Developmental Biology·Valentina GambacortaRaffaella Di Micco
Oct 20, 2019·International Journal of Molecular Sciences·Yanjun Zhang, Shengyou Huang
Jul 22, 2020·Seminars in Cell & Developmental Biology·Juliette FerrandSophie E Polo
Jan 8, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yunze LiuYi Zhang
Mar 12, 2021·Developmental Biology·Bridget T Jacques-FrickeLaura S Gammill
Jul 7, 2020·Organic Letters·Ludovic DecultotMatthew D Shair
Apr 10, 2021·Cold Spring Harbor Molecular Case Studies·Emilie LalondeMarilyn M Li
Apr 13, 2021·Breast Cancer Research and Treatment·Julia Y TsangGary M Tse
Apr 13, 2021·Experimental Dermatology·Gina Pacella, Brian C Capell
Sep 10, 2021·Genesis : the Journal of Genetics and Development·Julaine Roffers-AgarwalLaura S Gammill
Oct 31, 2021·Clinical Epigenetics·Chu XiaoJie He

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.