Nup98 regulation of histone methylation promotes normal gene expression and may drive leukemogenesis

Abstract

Nuclear pore proteins (Nups) interact with chromosomes to regulate gene expression and chromatin structure. A new study by Franks and colleagues (pp. 2222-2234) provides new mechanistic insight into the molecular basis by which Nup98 promotes gene activation in normal hematopoietic cells and how that process is altered by translocations to cause excess expression of developmental genes in leukemia.

Mutation analysis of second primary tumors in head and neck cancer in Taiwanese patients through next-generation sequencing

“…Nucleoporin 98kDa (NUP98) is a gene encoding a nucleoporin protein that functions in nuclear transport. It is associated with a wide array of hematopoietic malignancies [35]. Only POM121, a member of the NUP98 family, was reported in oral squamous cell carcinoma [36].…”

Novel ZFPL1::NUP98 fusion gene identified in an adult acute myeloid leukemia patient

“…HOXD13, NUP98::TOP1, and NUP98::NSD16. 6 From the data of both experimental models and patient samples, the leukemogenesis driven by NUP98 fusion oncoprotein is influenced by chromatin structure and gene expression alterations. Various cofactors are linked to NUP98 fusion oncoproteins to facilitate transcriptional changes, potentially through phase separation, in a way that may rely on the partner.…”

NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia

“…Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy driven largely by gene mutations and epigenetic modifications [ 1 , 2 ]. The Nucleoporin 98 kDa (NUP98) gene is a component of the nuclear pore complex that also plays a role as an intranuclear transcription scaffold [ 3 ]. Fusion genes involving NUP98 have been recognized in a wide array of hematologic malignancy, most commonly AML [ 4 ].…”