In vitro histone lysine methylation by NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L

Morishita, Masaki; Mevius, Damiaan E. H. F.; Luccio, Eric di

doi:10.1186/preaccept-3867013771372917

Cited by 21 publications

(27 citation statements)

References 54 publications

(151 reference statements)

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“…In the embryonal neural crest border region histone methyltransferase NSD3 activates MSX1 transcription probably via H3K4-methylation [52, 53]. In myoblasts and neural crest cells HDAC1 and HDAC3, respectively, inhibits MSX1 expression demonstrating an activating input of histone acetylation in these cell types [54, 55].…”

Section: Discussionmentioning

confidence: 99%

Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia

et al. 2016

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Recently, we identified deregulated expression of the B-cell specific transcription factor MEF2C in T-cell acute lymphoid leukemia (T-ALL). Here, we performed sequence analysis of a regulatory upstream section of MEF2C in T-ALL cell lines which, however, proved devoid of mutations. Unexpectedly, we found strong conservation between the regulatory upstream region of MEF2C (located at chromosomal band 5q14) and an intergenic stretch at 7q11 located between STAG3L4 and AUTS2, covering nearly 20 kb. While the non-coding gene STAG3L4 was inconspicuously expressed, AUTS2 was aberrantly upregulated in 6% of T-ALL patients (public dataset GSE42038) and in 3/24 T-ALL cell lines, two of which represented very immature differentiation stages. AUTS2 expression was higher in normal B-cells than in T-cells, indicating lineage-specific activity in lymphopoiesis. While excluding chromosomal aberrations, examinations of AUTS2 transcriptional regulation in T-ALL cells revealed activation by IL7-IL7R-STAT5-signalling and MEF2C. AUTS2 protein has been shown to interact with polycomb repressor complex 1 subtype 5 (PRC1.5), transforming this particular complex into an activator. Accordingly, expression profiling and functional analyses demonstrated that AUTS2 activated while PCGF5 repressed transcription of NKL homeobox gene MSX1 in T-ALL cells. Forced expression and pharmacological inhibition of EZH2 in addition to H3K27me3 analysis indicated that PRC2 repressed MSX1 as well. Taken together, we found that AUTS2 and MEF2C, despite lying on different chromosomes, share strikingly similar regulatory upstream regions and aberrant expression in T-ALL subsets. Our data implicate chromatin complexes PRC1/AUTS2 and PRC2 in a gene network in T-ALL regulating early lymphoid differentiation.

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Section: Discussionmentioning

confidence: 99%

Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia

et al. 2016

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“…As nucleosomal DNA contacts the NSD1 post-SET loop the active conformation is stabilized. This may explain the preference of NSD family members for nucleosomal H3K36 substrates compared to octamers and why NSD family HMTases methylate histone lysine residues other than H3K36 when octamers, recombinant histones or peptides are used as substrates (Li et al 2009b; Kudithipudi et al 2014; Morishita et al 2014). …”

Section: Identification and Function Of Nsdmentioning

confidence: 99%

“…NSD2 catalyzes the mono and dimethylation of H3K36 (Martinez-Garcia et al 2011; Morishita et al 2014). The first N-terminal PWWP domain of NSD2 specifically binds to H3K36me2 to stabilize NSD2 at chromatin, and the catalytic SET domain of NSD2 propagates this gene-activating mark to adjacent nucleosomes (Waggoner et al 2005; Kuo et al 2011; Martinez-Garcia et al 2011; Morishita et al 2014; Sankaran et al 2016).…”

Section: Identification and Function Of Nsd2mentioning

confidence: 99%

“…The first N-terminal PWWP domain of NSD2 specifically binds to H3K36me2 to stabilize NSD2 at chromatin, and the catalytic SET domain of NSD2 propagates this gene-activating mark to adjacent nucleosomes (Waggoner et al 2005; Kuo et al 2011; Martinez-Garcia et al 2011; Morishita et al 2014; Sankaran et al 2016). Similar to NSD1, the NSD2 post-SET domain is attached to the catalytic SET domain via an autoinhibitory loop region and inhibition is relieved upon nucleosome binding (Qiao et al 2011; Poulin et al 2016a).…”

Section: Identification and Function Of Nsd2mentioning

confidence: 99%

“…The sequence of NSD3-long from amino acids 703 to 1409 is highly conserved between NSD1 (68% identical) and NSD2 (55% identical) and contains the PHD, second PWWP and SET domain (Angrand et al 2001). Similar to NSD1 and NSD2, the carboxyl terminal region of NSD3-long that contains the catalytic preSET, SET and postSET domains is able to recognize and methylate histone H3 and H4 targets in vitro (Allali-Hassani et al 2014; Morishita et al 2014). However, unlike NSD2 a clear HMG box is missing from NSD3-long and the fourth PHD-type zinc finger contains an insertion of 49 amino acids (Stec et al 2001).…”

Section: Identification and Function Of Nsd3mentioning

confidence: 99%

See 2 more Smart Citations

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

Bennett

Swaroop

Troche

et al. 2017

Cold Spring Harb Perspect Med

143

184

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The Nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyl transferases 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. Since epigenetic therapy is an important emerging anti-cancer strategy, understanding the function of NSD family members may lead to the development of novel therapies.

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Protective effect of histone methyltransferase NSD3 on ISO‐induced cardiac hypertrophy

et al. 2019

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Nuclear receptor‐binding SET domain 3 (NSD3) is a lysine methyltransferase that plays important roles in multiple biological activities; however; its potential roles in the cardiovascular system remain unknown. In this study, we found that NSD3 expression is reduced by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of NSD3 attenuates ISO‐induced cardiomyocyte hypertrophy. Mechanistically, ISO treatment decreases H3K27me2/3 modifications on the atrial natriuretic factor (ANF) promoter by suppressing NSD3 and inhibits the association between NSD3 and bromodomain‐containing protein 4 (BRD4), thus suppressing the BRD4‐mediated H3K27ac modifications, which ultimately promote ANF transcription and cardiomyocyte hypertrophy. In conclusion, NSD3 decreases ANF expression and, thereby, attenuates ISO‐induced cardiomyocyte hypertrophy.

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In vitro histone lysine methylation by NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L

Cited by 21 publications

References 54 publications

Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia

Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia

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

Protective effect of histone methyltransferase NSD3 on ISO‐induced cardiac hypertrophy

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