The Role of Nuclear Receptor-Binding SET Domain Family Histone Lysine Methyltransferases in Cancer

Overview

Journal Cold Spring Harb Perspect Med

Specialty General Medicine

Date 2017 Feb 15

PMID 28193767

Citations 90

Authors

Richard L Bennett

Alok Swaroop

Catalina Troche

Jonathan D Licht

Affiliations

Soon will be listed here.

Abstract

The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1). These enzymes recognize and catalyze methylation of histone lysine marks to regulate chromatin integrity and gene expression. The growing number of reports demonstrating that alterations or translocations of these genes fundamentally affect cell growth and differentiation leading to developmental defects illustrates the importance of this family. In addition, overexpression, gain of function somatic mutations, and translocations of NSDs are associated with human cancer and can trigger cellular transformation in model systems. Here we review the functions of NSD family members and the accumulating evidence that these proteins play key roles in tumorigenesis. Because epigenetic therapy is an important emerging anticancer strategy, understanding the function of NSD family members may lead to the development of novel therapies.

Citing Articles

NSD3 protein methylation and stabilization transforms human ES cells into variant state.

Krishnamoorthy V, Hamdani F, Shukla P, Rao R, Anaitullah S, Biligiri K Life Sci Alliance. 2024; 8(3.

PMID: 39741006 PMC: 11707394. DOI: 10.26508/lsa.202402871.

Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.

Micallef I, Fenech K, Baron B Front Mol Biosci. 2024; 11:1455415.

PMID: 39703687 PMC: 11656028. DOI: 10.3389/fmolb.2024.1455415.

The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma.

Berardi A, Kaestner C, Ghitti M, Quilici G, Cocomazzi P, Li J Nucleic Acids Res. 2024; 53(1.

PMID: 39656918 PMC: 11724302. DOI: 10.1093/nar/gkae1121.

The oncogenic role of the NSD histone methyltransferases in head and neck and cervical cancers.

Ghiani L, Chiocca S Tumour Virus Res. 2024; 19:200301.

PMID: 39645166 PMC: 11683330. DOI: 10.1016/j.tvr.2024.200301.

Identification of potential methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design.

Shen Y, Zhang Y, Wu T, Zhang L, Belviso B Mol Divers. 2024; .

PMID: 39644397 DOI: 10.1007/s11030-024-11072-8.

References

Poulin M, Schneck J, Matico R, McDevitt P, Huddleston M, Hou W . Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36. Proc Natl Acad Sci U S A. 2016; 113(5):1197-201. PMC: 4747696. DOI: 10.1073/pnas.1521036113. View

Dawson M, Prinjha R, Dittmann A, Giotopoulos G, Bantscheff M, Chan W . Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011; 478(7370):529-33. PMC: 3679520. DOI: 10.1038/nature10509. View

Chen Y, McGee J, Chen X, Doman T, Gong X, Zhang Y . Identification of druggable cancer driver genes amplified across TCGA datasets. PLoS One. 2014; 9(5):e98293. PMC: 4038530. DOI: 10.1371/journal.pone.0098293. View

Waggoner D, Raca G, Welch K, Dempsey M, Anderes E, Ostrovnaya I . NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory. Genet Med. 2005; 7(8):524-33. DOI: 10.1097/01.GIM.0000178503.15559.d3. View

Wang G, Cai L, Pasillas M, Kamps M . NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol. 2007; 9(7):804-12. DOI: 10.1038/ncb1608. View

Berdasco M, Ropero S, Setien F, Fraga M, Lapunzina P, Losson R . Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci U S A. 2009; 106(51):21830-5. PMC: 2793312. DOI: 10.1073/pnas.0906831106. View

Berardi A, Quilici G, Spiliotopoulos D, Corral-Rodriguez M, Martin-Garcia F, Degano M . Structural basis for PHDVC5HCHNSD1-C2HRNizp1 interaction: implications for Sotos syndrome. Nucleic Acids Res. 2016; 44(7):3448-63. PMC: 4838375. DOI: 10.1093/nar/gkw103. View

Kuroda S, Suzuki S, Kurita A, Muraki M, Aoshima Y, Tanioka F . Cytological Features of a Variant NUT Midline Carcinoma of the Lung Harboring the NSD3-NUT Fusion Gene: A Case Report and Literature Review. Case Rep Pathol. 2015; 2015:572951. PMC: 4320876. DOI: 10.1155/2015/572951. View

Kim A, Kiefer C, Dean A . Distinctive signatures of histone methylation in transcribed coding and noncoding human beta-globin sequences. Mol Cell Biol. 2006; 27(4):1271-9. PMC: 1800709. DOI: 10.1128/MCB.01684-06. View

10.

Rosati R, La Starza R, Veronese A, Aventin A, Schwienbacher C, Vallespi T . NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with t(8;11)(p11.2;p15). Blood. 2002; 99(10):3857-60. DOI: 10.1182/blood.v99.10.3857. View

11.

Joshi A, Struhl K . Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell. 2005; 20(6):971-8. DOI: 10.1016/j.molcel.2005.11.021. View

12.

Bell O, Wirbelauer C, Hild M, Scharf A, Schwaiger M, MacAlpine D . Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in Drosophila. EMBO J. 2007; 26(24):4974-84. PMC: 2140113. DOI: 10.1038/sj.emboj.7601926. View

13.

Morris S, Shibata Y, Noma K, Tsukamoto Y, Warren E, Temple B . Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe. Eukaryot Cell. 2005; 4(8):1446-54. PMC: 1214526. DOI: 10.1128/EC.4.8.1446-1454.2005. View

14.

Marango J, Shimoyama M, Nishio H, Meyer J, Min D, Sirulnik A . The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood. 2007; 111(6):3145-54. PMC: 2265454. DOI: 10.1182/blood-2007-06-092122. View

15.

Sankaran S, Wilkinson A, Elias J, Gozani O . A PWWP Domain of Histone-Lysine N-Methyltransferase NSD2 Binds to Dimethylated Lys-36 of Histone H3 and Regulates NSD2 Function at Chromatin. J Biol Chem. 2016; 291(16):8465-74. PMC: 4861420. DOI: 10.1074/jbc.M116.720748. View

16.

Wu H, Zeng H, Lam R, Tempel W, Amaya M, Xu C . Structural and histone binding ability characterizations of human PWWP domains. PLoS One. 2011; 6(6):e18919. PMC: 3119473. DOI: 10.1371/journal.pone.0018919. View

17.

Min D, Ezponda T, Kim M, Will C, Martinez-Garcia E, Popovic R . MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC. Leukemia. 2012; 27(3):686-94. PMC: 3886861. DOI: 10.1038/leu.2012.269. View

18.

Angrand P, Apiou F, Stewart A, Dutrillaux B, Losson R, Chambon P . NSD3, a new SET domain-containing gene, maps to 8p12 and is amplified in human breast cancer cell lines. Genomics. 2001; 74(1):79-88. DOI: 10.1006/geno.2001.6524. View

19.

Rayasam G, Wendling O, Angrand P, Mark M, Niederreither K, Song L . NSD1 is essential for early post-implantation development and has a catalytically active SET domain. EMBO J. 2003; 22(12):3153-63. PMC: 162140. DOI: 10.1093/emboj/cdg288. View

20.

Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M, Schwartz R . A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature. 2009; 460(7252):287-91. DOI: 10.1038/nature08086. View