Preferred Label : Gene Silencing Pathway;
NCIt related terms : The PRC2 Complex Sets Long-term Gene Silencing Through Modification of Histone Tails;
Alternative definition : BIOCARTA: Packaging of DNA into chromatin allows the cell to store its genetic information
efficiently and has an important role in regulating gene expression. Recent studies
have revealed that chromatin structure can be altered by covalent modification of
nucleosomes, in particular acetylation and methylation of the core histone tails.
Histone hyperacetylation usually characterizes active chromatin, while histone deacetylation
correlates with repressed transcription. The Polycomb group (PcG) proteins are constituents
of evolutionary highly conserved molecular pathways regulating cell fate in several
tissues through diverse mechanisms, including 1) regulation of self-renewal/proliferation,
2) regulation of senescence/immortalization, 3) interaction with the initiation transcription
machinery, 4) interaction with chromatin-condensation proteins, 5) modification of
histones, 6) inactivation of paternal X chromosome, and 7) regulation of cell death.
The PcG proteins form multimeric protein complexes, PRC1 and PRC2 which are involved
in the heritable, stable repression of genes through modification of chromatin structure.
The EED-EZH2 complex (PRC 2 complex) acts early in development to set the stage for
the long term repressive PRC1 complex. The PRC2 complex is probably tethered to promoters
of affected genes through the interaction with specific DNA binding factors, such
as YY1, a zinc finger transcription factor that acts as both a positive and negative
regulator of transcription of cellular and viral genes. The EED-EZH2 proteins interact
with histone deacetylase core complex consisting of the histone deacetylases HDAC1
and HDAC2 and the histone binding proteins RbAp48 and RbAp46. Histone deacetylation
is probably a prerequisite for subsequent methylation, as histone tails cannot be
acetylated and methylated in the same time. The PRC complex specifically methylates
nucleosomal histone H3 at lysine 27, providing an epigenetic mark for binding of PRC1
complex. The histone methyltransferase activity of PRC2 is dependent on an intact
SET domain in the EZH2 protein. PRC1 complex blocks chromatin remodeling by SWI/SNF
factors, thus preventing transcription of repressed chromosome regions. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_prc2Pathway;
Origin ID : C39200;
UMLS CUI : C1517494;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
