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The relevance of polycomb group proteins to the development of psychiatric disorders

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Proteins belonging to the Polycomb Group (PcG) are a widely-recognized category of proteins that modify chromatin. PcG proteins and the triothorax group (TrxG) of proteins dynamically and antagonistically regulate gene… Click to show full abstract

Proteins belonging to the Polycomb Group (PcG) are a widely-recognized category of proteins that modify chromatin. PcG proteins and the triothorax group (TrxG) of proteins dynamically and antagonistically regulate gene expression with PcG proteins inhibiting, and the TrxG proteins stimulating, gene expression (Kuehner and Yao, 2019). PcG proteins are usually classified into a pair of distinct multiprotein groups, polycomb repressive complex 1 (PRC1) and PRC2 (Blackledge and Klose, 2021; Piunti and Shilatiford, 2021). The two classes have different enzymatic properties, although both are usually associated with silencing of transcription. PRC1 has E3 ubiquitin ligase action and in mammalian cells specifically catalyzes Lys118 and Lys119 of histone 2A, and mainly causes monoubiquitylation of them (Piunti and Shilatiford, 2021). PRC1 is not one complex, but comprises a minimum of eight varying complexes having different assortments of subunits. These subunits give differing biological functions to the complexes. The various complexes may be additionally classified as canonical or noncanonical members of PRC1, depending on their possessing a CBX protein or either of a pair of homologous proteins, namely RING1 and YY1 binding protein called RYBP, and YY1-associated factor 1 (YAF2), respectively. Non-canonical and canonical PRC1 complexes possess the molecule really interesting new gene 1A (RING1A), a protein, or its homologue, RING1B, that gives PRC1 its catalytic property (Piunti and Shilatiford, 2021). The PRC2 complex comprises a methyltransferase taking part in monomethylating, dimethylating, and trimethylating histone H3 Lys27. The enzymatic properties of PRC2 depend on the following subunits of the complex: 1) embryonic ectoderm development (EED), 2) suppressor of zeste 12 (SUZ12), and 3) enhancer of zeste homologue 2 (EZH2), or its homologue EXH1. In addition to RB binding protein 4 (RBBP4) or RBBP7, these subunits comprise the subunits of PRC2 that comprise its core, and along with several other subunits make up the recently elucidated complex variations of PRC2 (Piunti and Shilatiford, 2021). Transcriptional repression occurs due to the enzymatic functions of PRC1 and PRC2, particularly the generation of H2AK119ub and H3K27me3, respectively. However, both PRC1 and PRC2 have been shown to also have non-catalytic functions that facilitate repression of transcription (Piunti and Shilatiford, 2021). There is a sophisticated pathway OPEN ACCESS

Keywords: shilatiford 2021; piunti shilatiford; polycomb group

Journal Title: Frontiers in Cell and Developmental Biology
Year Published: 2022

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