Study of NSD2 using a dTAG system reveals their molecular mechanism and oncogenic implications in t(4;14) multiple myeloma - PubMed
3 hours ago
- #NSD2
- #multiple myeloma
- #epigenetics
- NSD2, a H3K36me2 methyltransferase, is aberrantly expressed in 10-15% of multiple myeloma (MM) due to t(4;14) translocation.
- The study used the dTAG system to degrade NSD2 and identified 307 transcriptional targets, showing its effects depend on SET domain activity.
- NSD2's H3K36me2 deposition antagonizes H3K27me3 levels, with half of its target genes regulated in an H3K27me3-dependent manner.
- CUT&Tag analysis revealed increased H3K27me3 at intergenic regions upon NSD2 depletion, suggesting NSD2 influences distal regulatory elements like enhancers.
- NSD2 target genes are enriched for oncogenic pathways and include transcription factors linked to neurodevelopment and acute leukemia.
- Eight identified transcription factors are known oncogenic drivers in acute leukemia or MM, highlighting NSD2's role in t(4;14) MM.