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Review
. 2017 Jun 1;7(6):a026708.
doi: 10.1101/cshperspect.a026708.

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

Richard L Bennett  1 , Alok Swaroop  1 , Catalina Troche  1 , Jonathan D Licht  1
Affiliations
Review

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

Richard L Bennett et al. Cold Spring Harb Perspect Med. .

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.

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Figures

Figure 1.
Figure 1.
Conserved structural domains in the nuclear receptor–binding SET domain (NSD) family of histone lysine methyltransferases. Protein domain assignments were calculated using a simple modular architecture research tool (SMART) and the following UniProtKB entries: NSD1-long, Q96L73-1; NSD1-short, Q96L73-2; NSD2-long, O96028-1; NSD2-short, O96028-3; RE-IIBP, O96028-4; NSD3-long, Q9BZ95-1; and NSD3-short, Q9BZ95-3. NSD3-WHISTLE domain assignments are from data in Kim et al. (2006).
Figure 2.
Figure 2.
Sequence alignment of the region of nuclear receptor–binding SET domain 3 (NSD3) required for BRD4 interaction with NSD1 and NSD2 reveals conserved regions amino terminal to the first PWWP domain. The region in NSD3 identified as being required for interaction with BRD4 (amino acids 100-263) was found to have significant homology with the corresponding region in NSD1 and NSD2. Sequence analysis was performed using CLC Sequence Viewer (Qiagen).
Figure 3.
Figure 3.
Proposed mechanism for targeting of nuclear receptor–binding SET domain (NSD) family proteins to specific chromatin loci.
See this image and copyright information in PMC

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