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| Status |
Public on Nov 29, 2011 |
| Title |
NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [RNAi] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
NSD2 (also named MMSET and WHSC1) is a histone lysine methyltransferase that is implicated in diverse diseases and commonly overexpressed in multiple myeloma due to a recurrent t(4;14) chromosomal translocation. However, the precise catalytic activity of NSD2 is obscure, preventing progress in understanding how this enzyme influences chromatin biology and myeloma pathogenesis. Here we show that dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of NSD2. Catalysis of H3K36me2 by NSD2 is sufficient for gene activation. In t(4;14)-positive myeloma cells, the normal genome-wide and gene-specific distribution of H3K36me2 is obliterated, creating a chromatin landscape that selects for a transcription profile favorable for myelomagenesis. Catalytically active NSD2 confers xenograft tumor formation and invasion capacity upon t(4;14)-negative cells and NSD2 promotes oncogenic transformation of primary cells in an H3K36me2-dependent manner. Together our findings establish H3K36me2 as the primary product generated by NSD2, and demonstrate that genomic disorganization of this canonical chromatin mark initiates oncogenic programming.
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| Overall design |
Genome-wide expression profiling of KMS11 cells stably transduced with control vector in comparison to two independent shRNAs against NSD2. Each cell line is tested in duplicate.
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| Contributor(s) |
Kuo AJ, Cheung P, Chen K, Zee BM, Lauring J, Xi Y, Park BH, Shi X, Kioi M, Garcia BA, Li W, Gozani O |
| Citation(s) |
22099308 |
| Submission date |
May 09, 2011 |
| Last update date |
Aug 16, 2018 |
| Contact name |
kaifu chen |
| E-mail(s) |
kaifuc@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Street address |
1 Baylor plaza, suite 450A
|
| City |
Houston |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE29305 |
NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming |
|
| Relations |
| BioProject |
PRJNA142877 |
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