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The role of EZH1 and EZH2 in development and cancer
Chul-Hwan Lee 1,* (Associate Professor), Yingying Li 1 (Graduate student), Hanbyeol Kim 1 (Graduate student), Seounghyun Eum 1 (Research worker), Kyumin Park 1 (Research worker), Soo Hyun Lee 1 (Graduate student)
1Department of Biomedical Sciences and 2Department of Pharmacology and 3BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, 03080, Korea.,
4Ischemic/hypoxic Disease Institute, Seoul National University College of Medicine Seoul, 03080, Korea.,
5Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.
Abstract
Polycomb Repressive Complex 2 (PRC2) exhibits key roles in mammalian development through its temporospatial repression of gene expression. EZH1 or EZH2 is the catalytic subunit of PRC2 that mediates the mono-, di- and tri-methylation of histone H3 lysine 27 (H3K27me1/2/3), H3K27me3 being a hallmark of facultative heterochromatin. PRC2 is a chromatin-modifying enzyme that is recruited to a limited number of “nucleation sites”, spreads H3K27 methylation and fosters chromatin compaction. EZH1 and EZH2 exhibit differences in their expression patterns, levels of histone methyltransferase activity (HMT) in the context of PRC2, and DNA/nucleosome binding activity. This suggests that their roles in heterochromatin formation are disparate. Dysregulation of PRC2 activity leads to aberrant gene expression and is implicated in cancer and developmental diseases. In this review, we discuss the distinct function of PRC2/EZH1 and PRC2/EZH2 in the early and late developmental stages. We then discuss the cancers associated with PRC2/EZH1 and PRC2/EZH2.
Abstract, Accepted Manuscript(in press) [Submitted on October 31, 2022, Accepted on November 29, 2022]
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