histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
methyltransferase
Methyltransferases are a large group of enzymes that all Methylation, methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which co ...
activity and primarily methylates
histone H3
Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a st ...
on
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...
27 (i.e. H3K27me3), a mark of transcriptionally silent
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...
. PRC2 is required for initial targeting of genomic region (PRC Response Elements or PRE) to be silenced, while PRC1 is required for stabilizing this
silencing
Silencing is a visual illusion in which a set of objects that change iluminancehuecellular memory of silenced region after
cellular differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...
histone H2A
Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.
The other histone proteins are: H1, H2B, H3 and H4.
Background
Histones are proteins that package DNA into nucleosomes. Hist ...
on lysine 119 (H2AK119Ub1). These
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s are required for long term epigenetic silencing of chromatin and have an important role in
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
differentiation and early
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
nic development. PRC2 are present in most
multicellular organism
A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism.
All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni ...
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
SET domain
Set, The Set, SET or SETS may refer to:
Science, technology, and mathematics Mathematics
*Set (mathematics), a collection of elements
* Category of sets, the category whose objects and morphisms are sets and total functions, respectively
Electr ...
with histone methyltransferase activity) and Rbbp4 (histone binding domain). PRC2 can bind to H3K27me3 and repress neighboring
nucleosome
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundame ...
s, thus spreading the repression.
PRC2 has a role in
X chromosome inactivation
X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a ...
, in maintenance of stem cell fate,Heurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z and in imprinting. Aberrant expression of PRC2 has been observed in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Both loss and gain-of-function mutations in PRC2 components have been identified in various human
cancers
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, suggesting complex roles of these components in malignancy.
Polycomb group genes directly and indirectly regulate the
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
response which acts as an anti-cancer barrier. The PRC2 complex appears to be present at sites of DNA double-strand breaks where it promotes repair of such breaks by
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
.
The PRC2 is
evolutionarily conserved
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...
, and has been found in mammals, insects, fungi, and plants.
In plants
In ''
Arabidopsis thaliana
''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land.
A winter ...
'', a plant
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
, several variants of the core subunits have been identified. Homologs of the Suz12 subunit are: Embryonic flower 2 (EMF2), reduced vernalization response 2 (VRN2), fertilization independent seed 2 (FIS2). There is one Eed homolog, fertilization independent endosperm (FIE). three Ezh1/Ezh2 homologs, curly leaf (CLF), swinger (SWN), medea (MEA), and one Rbbp4 homolog, multicopy suppressor of IRA1 (MSI1). Many other accessory components of PRC2 complex in Arabidopsis have been identifi
See also
*
Epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are ...