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J Biol Chem. December 4, 2009; 284 (49): 34283-95.

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 .

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: 4R37GM03712024 NIGMS NIH HHS , GM063716 NIGMS NIH HHS , P30 NS050276 NINDS NIH HHS , P30CA016087 NCI NIH HHS , S10 RR017990 NCRR NIH HHSHoward Hughes Medical Institute , 4R37GM037120-24 NIGMS NIH HHS , P30 CA016087 NCI NIH HHS , R01 GM063716 NIGMS NIH HHS , R37 GM037120 NIGMS NIH HHS

Genes referenced: alb celsr1 me1 me3 myc nsd1 nucb1 rab40b

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Angrand, 2001, Pubmed[+]

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