PXD056948-1

PXD056948 is an original dataset announced via ProteomeXchange.

Title	The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators
Description	Recurrent cancer-causing fusions of NUP98 produce higher-order assemblies known as condensates. How NUP98 oncofusion-driven condensates activate oncogenes remains poorly understood. Here, we investigate NUP98-PHF23, a leukemogenic chimera of the disordered FG-repeats-rich region of NUP98 and the H3K4me3/2-binding PHD finger domain of PHF23. Our integrated analyses using mutagenesis, proteomics, genomics, and condensate reconstitution demonstrate that the PHD domain targets condensates to H3K4me3/2-demarcated developmental genes while the FG repeats determine condensate composition and gene activation. The FG repeats are necessary to form condensates that partition a specific set of transcriptional regulators, notably the KMT2/MLL family of H3K4 methyltransferases, histone acetyltransferases and BRD4. The FG repeats are sufficient to partition these transcriptional regulators and activate a reporter when tethered to a locus. NUP98-PHF23 assembles the chromatin-bound condensates that partition multiple positive regulators, initiating a feed-forward loop of reading-and-writing active histone modifications. This network of interactions enforces an open chromatin landscape at proto-oncogenes, thereby driving cancerous transcriptional programs.
HostingRepository	PRIDE
AnnounceDate	2024-12-31
AnnouncementXML	Submission_2024-12-31_05:57:13.035.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056948
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stephanie Byrum
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-18 06:58:11	ID requested
⏵ 1	2024-12-31 05:57:13	announced

10.6019/PXD056948;

submitter keyword: H3K4me3, leukemia, histone modification, p300, KMT2/MLL,NUP98, WDR5, FG repeats, condensate, chromatin

Greg Wang
contact affiliation	1 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. 2 Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA 3 Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA 4 Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
contact email	greg.wang@duke.edu
lab head
Stephanie Byrum
contact affiliation	UAMS
contact email	sbyrum@uams.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056948
     1. Label: PRIDE project
     2. Name: The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators