biostudies-literatureFranks TMAmerican Cancer SocietyNational Cancer InstituteNCI NIH HHSNINDS NIH HHSHelmsley TrustNational Institutes of HealthNIHCancer Center Support GrantsRazavi Newman Integrative Genomics and Bioinformatics Core Facility of the Salk InstituteNIGMS NIH HHSGlenn Aging Foundation2222-2234https://www.ebi.ac.uk/biostudies/studies/S-EPMC5769767biostudies-literatureUnknown31(22)Recent studies have shown that a subset of nucleoporins (Nups) can detach from the nuclear pore complex and move into the nuclear interior to regulate transcription. One such dynamic Nup, called Nup98, has been implicated in gene activation in healthy cells and has been shown to drive leukemogenesis when mutated in patients with acute myeloid leukemia (AML). Here we show that in hematopoietic cells, Nup98 binds predominantly to transcription start sites to recruit the Wdr82-Set1A/COMPASS (complex of proteins associated with Set1) complex, which is required for deposition of the histone 3 Lys4 trimethyl (H3K4me3)-activating mark. Depletion of Nup98 or Wdr82 abolishes Set1A recruitment to chromatin and subsequently ablates H3K4me3 at adjacent promoters. Furthermore, expression of a Nup98 fusGenes & developmentNup98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells.PMC5769767P30CA014195PF-11-142-01-DMCR01 NS096786P30 014195P30 CA014195R01 GM098749R01GM098749McCloskey AHetzer MWBenner CShokirev MNRathore AFranks TMfalseNup98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells.Recent studies have shown that a subset of nucleoporins (Nups) can detach from the nuclear pore complex and move into the nuclear interior to regulate transcription. One such dynamic Nup, called Nup98, has been implicated in gene activation in healthy cells and has been shown to drive leukemogenesis when mutated in patients with acute myeloid leukemia (AML). Here we show that in hematopoietic cells, Nup98 binds predominantly to transcription start sites to recruit the Wdr82-Set1A/COMPASS (complex of proteins associated with Set1) complex, which is required for deposition of the histone 3 Lys4 trimethyl (H3K4me3)-activating mark. Depletion of Nup98 or Wdr82 abolishes Set1A recruitment to chromatin and subsequently ablates H3K4me3 at adjacent promoters. Furthermore, expression of a Nup98 fus2017-01-01T00:00:00Z2017 Nov2025-04-05T15:17:41.528Z2019-03-26T22:59:54ZS-EPMC57697672926948210.1101/gad.306753.117