PXD013390

PXD013390 is an original dataset announced via ProteomeXchange.

Title	Cxorf67-FLAG co-immunoprecipitation analysis from 293T cells
Description	The regulation of gene expression is controlled in part by post-translational modifications to histone proteins. Methylation at histone H3, lysine 27 (H3K27), which is catalyzed by Polycomb repressive complex 2 (PRC2), is associated with silenced chromatin. Previous studies have identified dysregulation of H3K27 methylation in pediatric diffuse intrinsic pontine gliomas (DIPGs), the majority of which feature mutation of lysine 27 to methionine. This “oncohistone” potently inhibits PRC2 activity and leads to a global reduction in H3K27 methylation. Similar to DIPG, posterior fossa type A (PFA) ependymomas also show low levels of H3K27 methylation. Although PFAs do not possess the H3K27M oncohistone mutation, they do show increased expression of Cxorf67. Interestingly, Cxorf67 contains a C-terminal sequence that resembles the sequence surrounding H3K27, and we find that this portion of Cxorf67 inhibits PRC2 activity to an even greater extent than the H3K27M oncohistone. Thus, we suggest re-naming Cxorf67 as EZHIP (Enhancer of Zeste Homologs Inhibitory Protein). Furthermore, when expressed in 293T cells, Cxorf67 interacts with several members of PRC2 and induces changes in H3K27 methylation patterns that mirror the changes in H3K27 methylation induced by expression of H3K27M. We propose that PFAs have dysregulated H3K27 methylation by a mechanism that involves inhibition of PRC2 by Cxorf67, which could drive tumorigenesis.
HostingRepository	PRIDE
AnnounceDate	2019-04-09
AnnouncementXML	Submission_2019-04-09_04:18:46.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013390
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Peder Lund
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Acetyl; Carbamidomethyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-08 02:17:13	ID requested
⏵ 1	2019-04-09 04:18:47	announced

Dataset with its publication pending

submitter keyword: Cxorf67, EZHIP, PRC2, epigenetics, H3K27me

Benjamin A. Garcia
contact affiliation	Dept. of Biochemistry and Biophysics, Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
contact email	bgarci@pennmedicine.upenn.edu
lab head
Peder Lund
contact affiliation	University of Pennsylvania
contact email	pederjlund@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013390
     1. Label: PRIDE project
     2. Name: Cxorf67-FLAG co-immunoprecipitation analysis from 293T cells