PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism

Siddhant U. Jain; Truman J. Do; Peder J. Lund; Andrew Q. Rashoff; Katharine L. Diehl; Marcin Cieslik; Andrea Bajic; Nikoleta Juretic; Shriya Deshmukh; Sriram Venneti; Tom W. Muir; Benjamin A. Garcia; Nada Jabado; Peter W. Lewis

doi:10.1038/s41467-019-09981-6

Nature Communications (May 2019)

PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism

Siddhant U. Jain,
Truman J. Do,
Peder J. Lund,
Andrew Q. Rashoff,
Katharine L. Diehl,
Marcin Cieslik,
Andrea Bajic,
Nikoleta Juretic,
Shriya Deshmukh,
Sriram Venneti,
Tom W. Muir,
Benjamin A. Garcia,
Nada Jabado,
Peter W. Lewis

Affiliations

Siddhant U. Jain: Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin
Truman J. Do: Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin
Peder J. Lund: Department of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania
Andrew Q. Rashoff: Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin
Katharine L. Diehl: Department of Chemistry, Princeton University
Marcin Cieslik: Department of Pathology, University of Michigan
Andrea Bajic: Department of Human Genetics, McGill University
Nikoleta Juretic: Department of Human Genetics, McGill University
Shriya Deshmukh: Department of Human Genetics, McGill University
Sriram Venneti: Department of Pathology, University of Michigan
Tom W. Muir: Department of Chemistry, Princeton University
Benjamin A. Garcia: Department of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania
Nada Jabado: Department of Human Genetics, McGill University
Peter W. Lewis: Department of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin

DOI: https://doi.org/10.1038/s41467-019-09981-6
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 14

Abstract

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PFA tumours express high levels of EZHIP (also known as CXORF67). Here the authors find that EZHIP directly interacts with the active site of EZH2 and is a competitive inhibitor of PRC2 and that EZHIP gives rise to H3K27me3 genomic profile similar to the K27M oncohistone.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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