The Polycomb and Trithorax page
history and introduction
||Polycomb and trithorax group proteins|
||Landmark Polycomb and trithorax discoveries|
|1:||Lanzuolo C, Orlando V.|
from the polycomb group proteins
Annu Rev Genet. 2012;46:561-89. doi: 10.1146/annurev-genet-110711-155603. Epub 2012 Sep 17.
PMID: 22994356 [PubMed - in process]
|2:||Pirrotta V, Li HB.|
view of nuclear Polycomb bodies.
Curr Opin Genet Dev. 2012 Apr;22(2):101-9. doi: 10.1016/j.gde.2011.11.004. Epub 2011 Dec 16. Review.
PMID: 22178420 [PubMed - indexed for MEDLINE]
|3:||Holec S, Berger F|
group complexes mediate developmental transitions in
Plant Physiol. 2012 Jan;158(1):35-43. doi: 10.1104/pp.111.186445. Epub 2011 Nov 15. Review. No abstract available.
PMID: 22086420 [PubMed - indexed for MEDLINE]
|4:||Bantignies F, Cavalli G|
group proteins: repression in 3D.
Trends Genet. 2011 Nov;27(11):454-64. doi: 10.1016/j.tig.2011.06.008. Epub 2011 Jul 25. Review.
PMID: 21794944 [PubMed - indexed for MEDLINE]
||Fisher CL, Fisher AG.|
states in pluripotent, differentiated, and
Curr Opin Genet Dev. 2011 Apr;21(2):140-6. doi: 10.1016/j.gde.2011.01.015. Review.
PMID: 21316216 [PubMed - indexed for MEDLINE]
|6:||Schuettengruber B, Martinez AM, Iovino N, Cavalli G.|
group proteins: switching genes on and keeping them
Nat Rev Mol Cell Biol. 2011 Nov 23;12(12):799-814. doi: 10.1038/nrm3230. Review.
PMID: 22108599 [PubMed - indexed for MEDLINE]
|7:||Margueron R, Reinberg D.|
Polycomb complex PRC2 and its mark in life.
Nature. 2011 Jan 20;469(7330):343-9. doi: 10.1038/nature09784. Review.
PMID: 21248841 [PubMed - indexed for MEDLINE]
|8:||Beisel C, Paro R.|
chromatin: comparing modes and mechanisms.
Nat Rev Genet. 2011 Feb;12(2):123-35. doi: 10.1038/nrg2932. Epub 2011 Jan 11. Review.
PMID: 21221116 [PubMed - indexed for MEDLINE]
|9:||Sawarkar R, Paro R.|
of developmental signaling at chromatin: the
Dev Cell. 2010 Nov 16;19(5):651-61. doi: 10.1016/j.devcel.2010.10.012. Review.
PMID: 21074716 [PubMed - indexed for MEDLINE]
the cancer switch: reciprocal roles of polycomb and
Nat Rev Cancer. 2010 Oct;10(10):669-82. doi: 10.1038/nrc2931. Review.
PMID: 20865010 [PubMed - indexed for MEDLINE]
|11:||Sauvageau M, Sauvageau G.|
group proteins: multi-faceted regulators of somatic
stem cells and cancer.
Cell Stem Cell. 2010 Sep 3;7(3):299-313. doi: 10.1016/j.stem.2010.08.002. Review.
PMID: 20804967 [PubMed - indexed for MEDLINE]
|12:||Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G.|
regulation by polycomb and trithorax proteins.
Cell. 2007 Feb 23;128(4):735-45.
PMID: 17320510 [PubMed - in process]
|This table lists PcG and trxG
proteins in humans and flies, as well as
proteins that may be involved at recruiting them
to their target genes. The left column indicates
whether the proteins are found in well-characterized
biochemical complexes. A brief note describes the
main function of each protein. In the Pubmed links
column, main papers describing the proteins are
hyperlinked. When too many papers have been
published on a given protein, I have put a link to a
review discussing it in more detail.
* indicates that the protein exist but its function in the PcG or trxG pathway is still not clear
Note: This table is constantly under revision. should you see mistakes or have updates, please send me an email
|Dsp1||HMGB2||Dsp1 is an HMG box protein. It
assists Pho in PcG recruitment at Drosophila PREs.
HMGB2 is involved in YY1 in silencing of D4Z4 repeats
||Fly Grh helps PcG recruitment at
||Fly Trl is involved for PcG
recruitment at some PREs although is classified as a
trxG protein. It is a Zn-finger sequence specific
protein that binds the GAGAG motif. It also contains a
BTP/POZ domain that is generally involved in
||Lola-like binds Trl and acts as a
||Psq co-purifies with components
of the PRC1 complex and binds the same sequences as
||Zeste found within PRC1 but also
linked to trxG-mediated activation
Identified in 2006
||Fly PhoRC binds
PREs and is involved in recruitment of PcG proteins to
PREs. Pho also forms a second complex named INO80,
likely to be involved in chromatin remodelling.
Pho can recruit the histone methyltransferase E(z) to the Ubx PRE. In vitro, it can also recruit PRC1 components to DNA independent on the action of E(z).
Whether PhoRC exist in human cells is unknown, but its homolog YY1 ca, recruit PcG proteins to target genes
||E2F6 forms two different
multimeric complexes containing PcG proteins, one with
RING1A, RING1B and MBLR, and the other one with EZH2,
E(PC) and Sin3A
||BCL6 is a BTB containing protein
(similar to Drosophila
Krüppel, but it is not known whether it is a
true homolog) that was suggested to recruit PcG
proteins to its target genes via the corepressor BCOR
|Human Retinoblastoma protein
represses genes in a PcG-dependent manner to block
cell proliferation. This pathway was not yet
identified in other organisms
||PLZF has been shown to bind to
the HoxD complex and to bind Polycomb proteins on
chromatin. This sequence specific DNA binding protein
contains a Zn-Finger domain and a BPB/POZ domain that
is generally involved in protein-protein interactions.
Plzf mutants strongly derepress the HoxD locus in the
embryonic hindlimb bud, PLZF binds to Bmi-1 and
recruits it to HoxD
H3K27 trimethylation activity characterized in 2002
|SET domain histone
methyltransferase, specific for H3K27.
||EED is required for the histone
methyltransferase activity of EZH2 within the PRC2
||Like EED, SUZ12 is a critical
minimal component required for enzymatic activity of
the PRC2 complexes. In Drosophila, Su(z)12 drives
nucleosome binding by PRC2.
Nurf55 and Su(z)12 form the minimal nucleosome binding
module of PRC2 in
|Pcl was found
in a PRC2 complex-subtype in flies, extracted from
late developmental stages. This complex has histone
deacetylation activity dependent on Rpd3. Pcl is
perfectly colocalized with PC in polytene chromosomes,
suggesting that it links PRC2 to PRC1.
||SIRT1 was found in a subtype of
PRC2 complex in human and flies, linking polycomb
silencing to histone deacetylation and cancer.
Identified in 1999.
PC identified as a reader of the H3K27me3 mark in 2002.
H2A ubiquitylation activity found in 2004.
||RING domain protein that is essential for the H2A ubiquitylation function of RING1B within the hPRC1L complex (see below)|
||RING1B is the catalytic subunit responsible for the H2A ubiquitylation within the hPRC1L complex. Sce/dRing is the corresponding protein in Drosophila|
|Chromo domain protein, reader of
the H3K27me3 mark. Required for silencing in flies.
In mammals, multiple homologs exert different functions by forming alternate PRC1 complexes (Refs a b c)
proteins are SAM and Zn-finger proteins that are
stoichiometric components of PRC1 and required for
silencing. In flies, Polyhomeotic has additional
phenotypes when compared to Polycomb, suggesting that
it may have additional functions.
Flag-tagged Ph and Psc were the starting components leading to the identification of the PRC1 complex in 1999.
|RING domain protein that is
essential for the H2A ubiquitylation function of
RING1B. BMI1 is a central component of the hPRC1L
complex that contains RING1A, RING1B, HPH2 and PC3. In
Drosophila, there is a second gene highly similar to
Psc, named Su(z)2,
which binds to similar sites in polytene chromosomes (Ref)
In mammals, multiple homologs exert different functions by forming alternate PRC1 complexes (Refs a b c)
Characterized in 1994
trxG function for Brm discovered in 1992
The Brm complex is a chromatin remodelling complex that uses the energy of ATP to remodel nucleosome structure and/or position, opening up chromatin structure. The Brm protein is the ATP-dependent engine of the complex. Moreover, this protein has a Bromodomain which drives binding to acetylated histones. In human, there are two subcomplexes, containing either BRM or BRG1. Brm complexes are involved in a large number of gene activation processes, probably beyond their function as antagonists of PcG-mediated silencing.
Identified in 1995
Reader of the H3K4me3 mark identified in 2006
The NURF complex, like the Brm complex, is a chromatin remodelling complex that uses the energy of ATP to remodel nucleosome structure and/or position, opening up chromatin structure. The ATP-dependent engine is Iswi/SNF2L in this case. In addition, this complex "reads" the histone H3K4me3 mark via the PHD finger of its largest subunit: Nurf-301/BPTF.
Identified in 2001
Trx function in H3K4 methylation found in 2004.
??? Human homologs exist (see below for Trx homologs MLL1-3), but the homolog complex has not been found. Instead, MLL complexes have been isolated, which are not known in flies.
The TAC1 complex seems to activate transcription of its target genes by stimulating transcription initiation as well as elongation. This occurs at Hox genes, but also at genes that were previously unknown to be regulated by trxG proteins like heat-shock genes. No TAC1-homologous complex has been isolated in human.
exist in human, but it is unknown whether they form a
||In Drosophila, Ash1
was shown to directly interact with dCBP and activate
Identified in 2002
??? Again, fly homologs of the MLL subunits exist, but no MLL complexes have been isolated in flies
These are the human Trx complexes. There are most likely multiple MLL complexes, each containing a different MLL subunit, which can function as a H3K4 methyltransferase. It is unclear whether the different MLLs have different functions. The WDR5 subunit binds to methyl H3K4 and stimulates further methylation by the SET domain of MLL. The ASH2L also regulates catalysis of trimethylation by MLL. In yeast, a similar complex exist, called COMPASS.
|PcG/trxG related proteins
|Lid was classified as a trxG
protein, but it has been later shown to possess H3K4
demethylase activity, which would fit better with a
PcG activity. This same enzymatic activity is also
found in the human proteins RBP2
|These proteins were found to be
able to demethylated tri- and dimethylated histone H3
K27. Biochemically, the mammalian components associate
with MLL (TrxG) complexes. In flies, dUTX colocalizes
with the elongating form of RNA pol II. Whether their
genetic function is to be classified in the trxG
remains to be determined.
Asx gene mutations have both PcG and trxG phenotypes.
||The Domino protein has a
DNA-dependent ATPase domain and belongs to the SWI/SNF
family. It is a member of the Tip60 complex, and is
involved in repression of Hox genes in flies. More
recently, it has also been involved in histone
replacement following DNA-damage.
||Chromosomal protein sharing some
sites with PC in polytene chromosomes in flies. Like
E(z), it behaves as a suppressor of heterochromatin
position effect variegation, suggesting that both
proteins play a role in heterochromatin in addition to
||Mi-2 is the ATP-dependent engine
of the NURD chromatin remodelling complex, which
couples nucleosome remodelling to histone
Mi-2 was proposed to make a link between
transcriptional repression in early embryogenesis and
PcG-mediated silencing in late embryogenesis
||Kismet is a chromodomain
containing ATP-dependent helicase. Originally
identified in flies as a suppressor of mutant Polycomb
phenotypes, it was later shown to be involved in RNA
pol II transcriptional elongation. Little is known
about the function of the human counterpart CHD7.
||ZMIZ1||Tonally is a fly Zn-finger
protein that, like kis, suppresses Pc mutant
phenotypes and is required for expression of Hox
genes. Not much is known about its putative human
||MED12L/TRAP230/TRALP||Drosophila Kohtalo and Skuld encode the homologs of the two largest subunits of "Mediator", a transcriptional coactivator complex. They interact directly and their mutants have the same phenotypes. Their trxG function has not been further characterized sofar.|
||Skuld/TRAP240. See comment to
Top PART 3. List of landmark discoveries
in the Polycomb and Trithorax field:
||Brief description of the main
||Ed Lewis's founding Polycomb paper
identifying a role for the Pc gene in the regulation of homeotic
||Characterization of the trithorax gene as a
regulator of homeotic gene expression
Role of PcG proteins in the maintenance of homeotic gene expression, i.e. in the process of "cellular memory"
||Antagonism between Polycomb and trithorax genes
||Polytene chromosome binding pattern of Pc
||Identification of Bmi-1, the first mammalian PcG
Role of Bmi-1 in Cancer
go: a! b!
||Involvement of Trithorax in leukemia
||Characterization of PREs in Drosophila
Chromatin IP of Polycomb
||Bmi-1 action as a bona fide mammalian PcG
||Analysis of PcG proteins in plants
PcG proteins and epigenetic regulation of gene expression by "cosuppression"
||Purification of the PRC1 complex
Role of PcG in cell proliferation
||trxG proteins and histone acetylation
||Link between PcG proteins and the basal
PcG proteins and genomic imprinting in mammals
||Characterization of the E(z)-Esc / PRC2 complex
- Histone methyltransferase activity
trxG proteins and histone methylation
go: a! b!
||Binding of the PC chromo domain to histone H3
methylated at Lysine 27
PcG proteins and X-inactivation
Polycomb as a Sumo E3 protein
go: a! b!
||PRC1 proteins mediate histone ubiquitination
Identification of a PRC3 complex related to PRC2 and identification of histone H1 methylation activity
||Identification of a link
between PcG proteins and DNA methylation
Role for PcG proteins in the phenomenon of transdetermination in Drosophila
go: a! b!
||Genome-wide mapping of the downstream target
sites for PcG proteins
||Discovery of H3K27me3 demethylases
||1- Crystal structure of EED reveals a mechamism
for maintenance of H3K27me3 through the cell cycle
(partially supports an earlier work by the Helin lab)
2- Identification and initial characterization of the first mammalian PREs
||Various links between PcG proteins and noncoding
RNAs (earlier work had pointed to a link between PcG
proteins and a ncRNA in X inactivation, but in 2010 the data
were broadly generalized and, in particular, SUZ12 was shown
to be an RNA-binding protein.
||a! b! c! d!|
||Identification of alternate
mammalian PRC1 complexes, suggesting that each of them may
have specific functions
||...will it be it your turn ?|
For obvious reasons, this list does not include
the work in our lab. For this, please go to the lab publications page.
Moreover, this list is certainly not perfect. If you have
important additions or updates that you wish to be included,
please write me an email.
in Spring 2015. Download
11 / 09 / 2015