Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer

Anne Laugesen; Jonas Westergaard Højfeldt; Kristian Helin

doi:10.1101/cshperspect.a026575

Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer

Anne Laugesen, Jonas Westergaard Højfeldt, Kristian Helin

DanStem

69 Citationer (Scopus)

Abstract

The chromatin environment is modulated by a machinery of chromatin modifiers, required for the specification and maintenance of cell fate. Many mutations in the machinery have been linked to the development and progression of cancer. In this review, we give a brief introduction to Polycomb group (PcG) proteins, their assembly into Polycomb repressive complexes (PRCs) and the normal physiological roles of these complexes with a focus on the PRC2. We review the many findings of mutations in the PRC2 coding genes, both loss-of-function and gain-of-function, associated with human cancers and discuss potential molecular mechanisms involved in the contribution of PRC2 mutations to cancer development and progression. Finally, we discuss some of the recent advances in developing and testing drugs targeting the PRC2 as well as emerging results from clinical trials using these drugs in the treatment of human cancers.

Originalsprog	Engelsk
Artikelnummer	a026575
Tidsskrift	Cold Spring Harbor Perspectives in Medicine
Vol/bind	6
Udgave nummer	9
ISSN	2157-1422
DOI	https://doi.org/10.1101/cshperspect.a026575
Status	Udgivet - sep. 2016

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AB - The chromatin environment is modulated by a machinery of chromatin modifiers, required for the specification and maintenance of cell fate. Many mutations in the machinery have been linked to the development and progression of cancer. In this review, we give a brief introduction to Polycomb group (PcG) proteins, their assembly into Polycomb repressive complexes (PRCs) and the normal physiological roles of these complexes with a focus on the PRC2. We review the many findings of mutations in the PRC2 coding genes, both loss-of-function and gain-of-function, associated with human cancers and discuss potential molecular mechanisms involved in the contribution of PRC2 mutations to cancer development and progression. Finally, we discuss some of the recent advances in developing and testing drugs targeting the PRC2 as well as emerging results from clinical trials using these drugs in the treatment of human cancers.

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DO - 10.1101/cshperspect.a026575

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SN - 2157-1422

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JO - Cold Spring Harbor Perspectives in Medicine

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Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer

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