PTK6

Polycomb Repressive Complex 2 (PRC2)

Polycomb Repressive Complex 2 (PRC2) is a highly conserved protein complex that plays a crucial role in the regulation of gene expression through chromatin modification. It is part of the Polycomb group (PcG) proteins, which are essential for maintaining the transcriptional repression of genes involved in development and differentiation.

Structure and Components

PRC2 is composed of several core subunits, including:

• Enhancer of Zeste Homolog 2 (EZH2): The catalytic subunit responsible for the methylation of histone H3 on lysine 27 (H3K27me3), a key epigenetic mark associated with gene repression.
• Suppressor of Zeste 12 (SUZ12): A core component that is essential for the stability and activity of the complex.
• Embryonic Ectoderm Development (EED): A subunit that recognizes the H3K27me3 mark and helps propagate the repressive signal.
• Retinoblastoma-binding protein 4/7 (RBBP4/7): These proteins are involved in chromatin remodeling and histone binding.

Function

PRC2 primarily functions to repress gene expression by catalyzing the trimethylation of histone H3 at lysine 27 (H3K27me3). This modification leads to a more compact chromatin structure, thereby preventing the transcriptional machinery from accessing the DNA.

Role in Development

PRC2 is crucial for the regulation of genes involved in embryonic development and cell fate determination. It helps maintain the pluripotency of stem cells and is involved in the differentiation of various cell types by repressing lineage-specific genes until they are needed.

Role in Disease

Dysregulation of PRC2 activity has been implicated in various diseases, particularly cancer. Overexpression or mutations in components of PRC2, such as EZH2, can lead to aberrant silencing of tumor suppressor genes, contributing to oncogenesis.

Mechanism of Action

PRC2 is recruited to specific genomic loci through interactions with long non-coding RNAs (lncRNAs), DNA-binding proteins, and other chromatin-associated factors. Once recruited, EZH2 catalyzes the addition of methyl groups to H3K27, establishing a repressive chromatin environment.

Research and Therapeutic Implications

Given its role in gene regulation and disease, PRC2 is a target for therapeutic intervention. Inhibitors of EZH2 are being developed and tested in clinical trials for the treatment of cancers with PRC2 dysregulation.

Also see

• Polycomb group proteins
• Histone modification
• Epigenetics
• Gene expression regulation
• Chromatin remodeling

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