NSD1 (E2U6H) Rabbit mAb #51076

Nuclear receptor SET domain-containing protein 1 (NSD1) is a member of the NSD family of histone methyltransferases, including WHSC1/NSD2 and WHSC1L1/NSD3. NSD1 specifically catalyzes mono- and di-methylation of histone H3 at Lys36 (H3K36me), a mark that is typically associated with transcriptionally active regions of the genome (1,2). NSD1 is expressed as two isoforms: a predominantly expressed short isoform of roughly 2,400 amino acids, and a less abundant long isoform of nearly 2,700 amino acids (3). NSD1 is required for proper embryonic development, as deletion of NSD1 is embryonic lethal in mice (4). Mutations in NSD1 are also believed to be the major cause of Sotos syndrome, an overgrowth disorder characterized by pre- and post-natal overgrowth, macrocephaly, advanced bone age, and developmental delay (5-7). NSD1 mutations have additionally been documented in two related overgrowth disorders, Weaver syndrome and Beckwith-Wiedemann syndrome, albeit less frequently (6-8). NSD1 is also mutated or has altered expression in several types of cancer. For instance, NSD1 is upregulated in metastatic prostate cancer and hepatocellular carcinoma (HCC) compared to healthy tissue (9,10). Loss-of-function mutations have also been observed for NSD1 in head and neck squamous cell carcinomas (HNSCCs), and the NSD1 gene is epigenetically silenced in neuroblastoma and glioma cells (11,12). NSD1, therefore, appears to exert tumor suppressive or promoting functions depending on cellular context, either through promoting the expression of tumor suppressor or oncogenic proteins, respectively (13).