The Polycomb Complex PRC2 and its Mark in Life

The Polycomb Complex PRC2 and its Mark in Life

2011 January 20 | Raphaël Margueron and Danny Reinberg
The Polycomb Complex PRC2 and its Mark in Life PRC2 is a key complex in the Polycomb Group (PcG) proteins that regulate gene expression during development and maintain appropriate patterns of homeotic gene expression. PRC2 is responsible for the methylation of lysine 27 of histone H3 (H3K27me2/3) through its enzymatic subunits Ezh1 and Ezh2. PRC1, another complex, mono-ubiquitylates lysine 119 of histone H2A (H2AK119ub) via the ubiquitin ligases Ring1a or Ring1b. PRC2 and PRC1 are often both required to maintain gene repression. PRC2 is well conserved throughout evolution and its presence in various unicellular eukaryotes suggests it could have existed in the last common unicellular ancestor. However, it was lost at times during evolution, as exemplified by the cases of S. Pombe or S. Cerevisae. In mammals, PRC2 has two copies of Ezh1 and Ezh2, with Ezh1 being present in dividing and differentiated cells and Ezh2 only in actively dividing cells. PRC2-Ezh1 and -Ezh2 exhibit distinct chromatin binding properties. In contrast, PRC2 evolved towards a greater complexity in plants, with species such as Thaliana having up to 12 homologs of PRC2 components. PRC2 comprises more than 4 components, including Ezh1/2, Suz12, Eed and RbAp46/48, as well as AEBP2, Pcls and Jarid2. These components play various roles in PRC2 function, including enhancing enzymatic activity, regulating gene expression, and recruiting PRC2. PRC2 is involved in the regulation of a broad array of biological processes and establishes regulatory cues that are stable and propagated throughout development. However, these cues can be subject to adjustment at each step of differentiation or in response to external stimuli. PRC2 is required for the maintenance of pluripotency and its inactivation leads to the loss of pluripotency-specific factors. PRC2 is also involved in cancer, with its components being upregulated in various diseases such as melanoma, lymphoma, breast and prostate cancer. Ezh2 has been reported to be a marker of the aggressive stages of prostate and breast malignancies, and its overexpression promotes neoplastic transformation of normal prostatic cells and hyperplasia in breast epithelium. PRC2 is also involved in the regulation of gene expression during differentiation, with its inactivation leading to defects in lineage commitment and terminal differentiation. PRC2 is required for the acquisition of pluripotency and its inactivation leads to the failure to induce the reprogramming of BThe Polycomb Complex PRC2 and its Mark in Life PRC2 is a key complex in the Polycomb Group (PcG) proteins that regulate gene expression during development and maintain appropriate patterns of homeotic gene expression. PRC2 is responsible for the methylation of lysine 27 of histone H3 (H3K27me2/3) through its enzymatic subunits Ezh1 and Ezh2. PRC1, another complex, mono-ubiquitylates lysine 119 of histone H2A (H2AK119ub) via the ubiquitin ligases Ring1a or Ring1b. PRC2 and PRC1 are often both required to maintain gene repression. PRC2 is well conserved throughout evolution and its presence in various unicellular eukaryotes suggests it could have existed in the last common unicellular ancestor. However, it was lost at times during evolution, as exemplified by the cases of S. Pombe or S. Cerevisae. In mammals, PRC2 has two copies of Ezh1 and Ezh2, with Ezh1 being present in dividing and differentiated cells and Ezh2 only in actively dividing cells. PRC2-Ezh1 and -Ezh2 exhibit distinct chromatin binding properties. In contrast, PRC2 evolved towards a greater complexity in plants, with species such as Thaliana having up to 12 homologs of PRC2 components. PRC2 comprises more than 4 components, including Ezh1/2, Suz12, Eed and RbAp46/48, as well as AEBP2, Pcls and Jarid2. These components play various roles in PRC2 function, including enhancing enzymatic activity, regulating gene expression, and recruiting PRC2. PRC2 is involved in the regulation of a broad array of biological processes and establishes regulatory cues that are stable and propagated throughout development. However, these cues can be subject to adjustment at each step of differentiation or in response to external stimuli. PRC2 is required for the maintenance of pluripotency and its inactivation leads to the loss of pluripotency-specific factors. PRC2 is also involved in cancer, with its components being upregulated in various diseases such as melanoma, lymphoma, breast and prostate cancer. Ezh2 has been reported to be a marker of the aggressive stages of prostate and breast malignancies, and its overexpression promotes neoplastic transformation of normal prostatic cells and hyperplasia in breast epithelium. PRC2 is also involved in the regulation of gene expression during differentiation, with its inactivation leading to defects in lineage commitment and terminal differentiation. PRC2 is required for the acquisition of pluripotency and its inactivation leads to the failure to induce the reprogramming of B
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Understanding The Polycomb complex PRC2 and its mark in life