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XB-ART-40836
J Biol Chem December 4, 2009; 284 (49): 34283-95.
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The target of the NSD family of histone lysine methyltransferases depends on the nature of the substrate.

Li Y , Trojer P , Xu CF , Cheung P , Kuo A , Drury WJ , Qiao Q , Neubert TA , Xu RM , Gozani O , Reinberg D .


Abstract
The NSD (nuclear receptor SET domain-containing) family of histone lysine methyltransferases is a critical participant in chromatin integrity as evidenced by the number of human diseases associated with the aberrant expression of its family members. Yet, the specific targets of these enzymes are not clear, with marked discrepancies being reported in the literature. We demonstrate that NSD2 can exhibit disparate target preferences based on the nature of the substrate provided. The NSD2 complex purified from human cells and recombinant NSD2 both exhibit specific targeting of histone H3 lysine 36 (H3K36) when provided with nucleosome substrates, but histone H4 lysine 44 is the primary target in the case of octamer substrates, irrespective of the histones being native or recombinant. This disparity is negated when NSD2 is presented with octamer targets in conjunction with short single- or double-stranded DNA. Although the octamers cannot form nucleosomes, the target is nonetheless nucleosome-specific as is the product, dimethylated H3K36. This study clarifies in part the previous discrepancies reported with respect to NSD targets. We propose that DNA acts as an allosteric effector of NSD2 such that H3K36 becomes the preferred target.

PubMed ID: 19808676
PMC ID: PMC2797197
Article link: J Biol Chem
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: alb celsr1 me1 me3 myc nsd1 nsd2 nucb1 rab40b
GO keywords: chromatin maintenance
Antibodies: H3K27me3 Ab11 H3f3a Ab34 H4K20me2 Ab2 HIST1H3A Ab3 Hist1h4a Ab1 Histone H4 Ab4 Histone H4 Ab5 Tubb2b Ab7

Disease Ontology terms: Wolf-Hirschhorn syndrome [+]
OMIMs: BREAST CANCER [+]

Article Images: [+] show captions
References [+] :
Angrand, NSD3, a new SET domain-containing gene, maps to 8p12 and is amplified in human breast cancer cell lines. 2001, Pubmed