The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797197/ https://www.ncbi.nlm.nih.gov/pubmed/19808676 http://dx.doi.org/10.1074/jbc.M109.034462 |
_version_ | 1782175598847721472 |
---|---|
author | Li, Yan Trojer, Patrick Xu, Chong-Feng Cheung, Peggie Kuo, Alex Drury, William J. Qiao, Qi Neubert, Thomas A. Xu, Rui-Ming Gozani, Or Reinberg, Danny |
author_facet | Li, Yan Trojer, Patrick Xu, Chong-Feng Cheung, Peggie Kuo, Alex Drury, William J. Qiao, Qi Neubert, Thomas A. Xu, Rui-Ming Gozani, Or Reinberg, Danny |
author_sort | Li, Yan |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2797197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-27971972009-12-23 The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate Li, Yan Trojer, Patrick Xu, Chong-Feng Cheung, Peggie Kuo, Alex Drury, William J. Qiao, Qi Neubert, Thomas A. Xu, Rui-Ming Gozani, Or Reinberg, Danny J Biol Chem Transcription, Chromatin, and Epigenetics 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. American Society for Biochemistry and Molecular Biology 2009-12-04 2009-10-06 /pmc/articles/PMC2797197/ /pubmed/19808676 http://dx.doi.org/10.1074/jbc.M109.034462 Text en © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Transcription, Chromatin, and Epigenetics Li, Yan Trojer, Patrick Xu, Chong-Feng Cheung, Peggie Kuo, Alex Drury, William J. Qiao, Qi Neubert, Thomas A. Xu, Rui-Ming Gozani, Or Reinberg, Danny The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title | The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title_full | The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title_fullStr | The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title_full_unstemmed | The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title_short | The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate |
title_sort | target of the nsd family of histone lysine methyltransferases depends on the nature of the substrate |
topic | Transcription, Chromatin, and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797197/ https://www.ncbi.nlm.nih.gov/pubmed/19808676 http://dx.doi.org/10.1074/jbc.M109.034462 |
work_keys_str_mv | AT liyan thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT trojerpatrick thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT xuchongfeng thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT cheungpeggie thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT kuoalex thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT drurywilliamj thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT qiaoqi thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT neubertthomasa thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT xuruiming thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT gozanior thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT reinbergdanny thetargetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT liyan targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT trojerpatrick targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT xuchongfeng targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT cheungpeggie targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT kuoalex targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT drurywilliamj targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT qiaoqi targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT neubertthomasa targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT xuruiming targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT gozanior targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate AT reinbergdanny targetofthensdfamilyofhistonelysinemethyltransferasesdependsonthenatureofthesubstrate |