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Series GSE274250 Query DataSets for GSE274250
Status Public on Jan 15, 2025
Title The C-terminal of NSD2 regulates transcription of cell adhesion genes in multiple myeloma
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The overexpression of the histone methyltransferase NSD2 (MMSET) in multiple myeloma (MM) patients plays a significant role in the development of this specific subtype of disease. Through the expansion of gene activation associated H3K36me2 and suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR and ITC techniques, we demonstrate that the tandem PHD domain of NSD2 (PHDvC5HCHNSD2) acts as a reader for both unmodified histone H3K4 and three-methylated H3K27, making it the first PHD tandem cassette known to decode the methylation status of H3K27. We present a three-dimensional model of the complex based on NMR data and molecular dynamics simulations. Importantly, expression of mutants of PHDvC5HCHNSD2, designed to impair binding to the histone H3 tail in NSD2 deficient cells, leads to decreased activation of adhesive properties and cell adhesion genes and a decrease in corresponding H3K27ac signal at promoters. Moreover, expression of PHDvC5HCH mutant forms of NSD2 result in incomplete loss of H3K27 methylation throughout the genome compared to expression of wild-type NSD2. Collectively, these data indicate that PHDvC5HCH of NSD2 plays an important role in modulating gene expression and chromatin modification, thus opening new opportunities for pharmacological intervention.
 
Overall design 10 million TKO cells that expressed either wild type or mutant forms of the histone methyltransferase NSD2 were harvested and ChIPmentation performed to measure how mutant NSD2 may alter chromatin marks.
 
Contributor(s) Kaestner C, Licht J, Musco G
Citation(s) 39656918
Submission date Aug 07, 2024
Last update date Jan 15, 2025
Contact name Jonathan Licht
E-mail(s) jdlicht@ufl.edu
Organization name University of Florida
Department UF Health Cancer Center
Street address 2033 Mowry Road
City Gainesville
State/province Florida
ZIP/Postal code 32610
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM8446251 D1240A-H3K27me3-Rep1
GSM8446252 D1240A-H3K27me3-Rep2
GSM8446253 D1240A-H3K4me3
Relations
BioProject PRJNA1145459

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE274250_D1240A-H3K27me3.peaks.bed.gz 58.7 Kb (ftp)(http) BED
GSE274250_D1240A-H3K4me3.peaks.bed.gz 173.7 Kb (ftp)(http) BED
GSE274250_F1295A-H3K27me3.peaks.bed.gz 55.9 Kb (ftp)(http) BED
GSE274250_F1295A-H3K4me3.peaks.bed.gz 186.1 Kb (ftp)(http) BED
GSE274250_TKO-H3K27me3.peaks.bed.gz 153.1 Kb (ftp)(http) BED
GSE274250_TKO-H3K4me3.peaks.bed.gz 164.7 Kb (ftp)(http) BED
GSE274250_WT-H3K27me3.peaks.bed.gz 100.4 Kb (ftp)(http) BED
GSE274250_WT-H3K4me3.peaks.bed.gz 183.0 Kb (ftp)(http) BED
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