PXD036192

PXD036192 is an original dataset announced via ProteomeXchange.

Title	MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain
Description	Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the linker DNA and binding of WH2 to the dyad of the nucleosome, with the latter being further modulated by the neighboring domain DPF and autoacetylation of MORF. The discovery of WHs in MORF and MOZ and their DNA binding functions could open a new avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:42:45.214.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036192
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Ebmeier
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-21 03:58:23	ID requested
1	2023-03-11 04:44:10	announced
⏵ 2	2023-11-14 08:42:52	announced	2023-11-14: Updated project metadata.

10.6019/PXD036192;

Becht DC, Klein BJ, Kanai A, Jang SM, Cox KL, Zhou BR, Phanor SK, Zhang Y, Chen RW, Ebmeier CC, Lachance C, Galloy M, Fradet-Turcotte A, Bulyk ML, Bai Y, Poirier MG, C, ô, t, é J, Yokoyama A, Kutateladze TG, MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain. Nat Commun, 14(1):697(2023) [pubmed]

submitter keyword: MORF MOZ CpG islands

Tatiana G. Kutateladze
contact affiliation	1Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
contact email	tatiana.kutateladze@cuanschutz.edu
lab head
Christopher Ebmeier
contact affiliation	University of Colorado Boulder
contact email	christopher.ebmeier@colorado.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036192
     1. Label: PRIDE project
     2. Name: MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain