transcription factor - chromo domain - Polycomb group - chromatin associated protein - involved in gene silencing chromatin binding protein that interacts with histone H3K27me3 - Pc target genes are predominantly transcription factors or receptors that control cell fate and most developmental decisions
Gene model reviewed during 5.45
There is only one protein coding transcript and one polypeptide associated with this gene
390 (aa); 44 (kD predicted)
A variation on the in vivo formaldehyde cross-linking technique was used to map Pc-interacting sites along the chromatin in the BX-C region. Pc was found to quantitatively cover large regulatory regions of repressed BX-C genes. Pc did not bind the transcriptionally active Abd-B region.
Pc protein and polyhomeotic protein are coprecipitated by antibodies to either showing that they are constituents of a multimeric protein complex. Pc and polyhomeotic complexes can be coprecipitated over the entire period of embryogenesis. The molecular weight of the complex is ~2-5x103kD. Double-immunofluorescence labeling was used to show that Pc protein and polyhomeotic protein have exactly the same binding patterns on polytene chromosomes.
Pc protein is associated with ~60 sites on the
polytene chromosomes. It is associated with loci shown to interact with
Pc by genetic methods. It is abundant at the ANT-C and the BX-C and is
in salivary glands is encoded by a 1.0kb Pc transcript and is smaller
than the 390aa Pc protein.
Component of PRC1 complex, which contains many PcG proteins like Pc, ph, Scm, Psc, Sce and also chromatin-remodeling proteins such as histone deacetylases. This complex is distinct from the Esc/E(z) complex, at least composed of esc, E(z), Su(z)12, HDAC1/Rpd3 and Caf1-55. The 2 complexes however cooperate and interact together during the first 3 hours of development to establish PcG silencing (PubMed:11493925, PubMed:11583617). Interacts with stx; the interaction targets Pc for ubiquitin-independent proteasomal degradation (PubMed:27326929). Interacts with Nup93-1 (PubMed:31784359).
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Pc using the Feature Mapper tool.
The Pc protein accumulates in the region of the bithorax complex genes on polytene chromosomes from anterior regions of larval fat bodies where the homeotic genes are repressed.
The distribution of polyhomeotic protein and Pc protein is nearly indistinguishable in embryos.
Pc protein is expressed in ovaries and during all stages of embryogenesis. Protein levels increase with developmental time in embryos. Two phases of Pc expression are observed in ovaries. First, substantial Pc protein is found in the germarium and in stage S1 and S2 follicles. Protein levels decline during stages S3-S8 and rise again in stages S9 and S10. In the germline, most of the protein is found in the polyploid nurse cell nuclei. Some Pc protein is deposited in the oocyte but none is observed in the nucleus. A very dynamic pattern of expression involving overlapping gradients is observed in follicle cells during stages S10-S14. In embryos, Pc transcripts are homogenously distributed over the length of the embryo at the cellular blastoderm stage and in germ band extended embryos. In late stage embryos, transcripts are found predominantly in the CNS. Particularly strong expression is observed in the supra-, suboesophageal and anterior thoracic ganglia. Strong staining is also observed in the pharynx, salivary glands, and other internal tissues.
GBrowse - Visual display of RNA-Seq signalsView Dmel\Pc in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Haploinsufficient locus (not associated with strong haplolethality or haplosterility).
DNA-protein interactions: genome-wide binding profile assayed for Pc protein in Kc167 cells; see Chromatin_types_NKI collection report. Individual protein-binding experiments listed under "Samples" at GEO_GSE22069 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22069).
Pc is required for normal neuroblast survival and proliferation in postembryonic central nervous system development.
Pc is required for for the maintenance of dendritic fields in class IV dendrite arborisation (da) neurons.
dsRNA made from templates generated with primers directed against Pc used to treat S2 cells results in a decreased proportion of cells in G1 and S phase, with an accompanying increase in G2/M cells. This modification of the cell cycle profile occurs in the absence of any apparent growth defect.
Mutant allele fails to complement a QTL affecting male mating behaviour.
Pc-G proteins can silence gene expression at a large number of chromosomal locations, affecting both enhancer-activated and basal w transcription. Repression is observed even with separation distances of up to 3.0kb between target promoters and binding sites for tethered Pc-G proteins.
Pc protein is associated with genes silenced as part of the cosuppression phenomenon.
Pc, Scm, Psc, ph-p and ph-d contribute to the PRC1 (Polycomb repressive complex 1). PRC1 directly antagonizes ATP-dependent remodeling of nucleosomal arrays in a purified system and may directly modulate (and be modified by) SWI/SNF (brm/mor) activity.
Evidence of physical interaction between esc and E(z) in vitro and in vivo and coimmunoprecipitation in vivo suggests the proteins are direct partners in Pc-G mediated repression and this relationship has been evolutionarily conserved.
ph-p, Psc and Pc proteins coimmunoprecipitate from nuclear extracts. Interacting domains are identified and delimited using the two-hybrid system, the interactions are shown to be direct by using an in vitro binding assay.
The Pc and trx gene products bind to PRE target sequences by cellular blastoderm, when the bithorax complex transcription begins. At the same stage trx but not Pc gene product is strongly associated with core promoters. At germ band extension, the time of derepression in Pc mutants, Pc gene product is found outside core PREs.
Abd-B MCP725 element is a silencer that functions throughout proliferation of the imaginal discs. MCP725-mediated silencing requires the Pc and Pcl proteins (it is likely that other members of the PcG also interact with the MCP725 silencer).
Silencing activity of the iab-7PRE in the bithorax complex is dependent upon proteins from the Polycomb group.
The chromodomain of Pc is necessary for protein-protein interactions within a Pc-polyhomeotic complex. In addition, Psc protein coimmunoprecipitates Pc and polyhomeotic indicating they are members of a common multimeric protein complex. These three proteins are associated with identical regulatory elements of en in tissue culture cells and differentially distributed on regulatory sequences of inv.
The distribution of Pc protein on the bithorax complex of Drosophila tissue culture cells has been mapped. The protein is not distributed homogeneously on the regulatory regions of the repressed Ubx and abd-A genes, but is highly enriched at discrete sequence elements, many of which coincide with previously mapped Pc response elements (PREs). Trl protein is also bound at those PREs which contain Trl consensus-binding sites.
Using reporter gene constructs the Pc group response elements (PRE) behaves as an orientation-dependent silencer capable of inducing mosaic gene expression on neighbouring genes.
In an effort to subdivide the Pc-group genes functionally, the phenotypes of adult flies heterozygous for every pairwise combination of Pc-group mutation were examined. Asx, Pc, Pcl, Psc, Scm and Sce have similar functions in some imaginal tissues. Genetic interactions have been demonstrated between esc, Asx, E(Pc), Pcl, E(z) and sxc. Most duplications of Pc-group genes neither exhibit anterior transformations nor suppress the extra sex comb phenotype of Pc-group mutations, suggesting that not all Pc-group genes behave as predicted by the mass action model.
Proper regulation of both trx and Pc can be established by transient assays with a haploid cell line expressing Ubx promoters fused to a Ecol\lacZ reporter gene. This system has been used to map the regulatory sequences in the Ubx promoter to a 440bp region. The Ubx proximal promoter is essential for trx-dependent activation.
The negative autoregulation of ph-p starts at the blastoderm stage and is partly mediated by a transvection effect. As the number of functional copies of ph-p increases a concomitant reduction of the transcription in each copy is observed. This regulation is ensured positively by the trx group and negatively by the Pc group gene products.
Pc acts as a transcriptional silencer in embryos if tethered to reporter genes by the DNA binding domain of Scer\GAL4 (as a Scer\GAL4-Pc fusion gene). Silencing by Scer\GAL4-Pc requires the C-terminal portion, but not the chromodomain.
A chimeric Su(var)205-Pc protein (the chromo domain of Pc in the context of Su(var)205) causes mislocalisation of Su(var)205 to Pc binding sites and expression in transgenic flies promotes heterochromatin mediated gene silencing. Results support the view that the chromo domain homology reflects a common mechanistic basis for homeotic and heterochromatic silencing.
Members of the Pc group function as potent repressors in mammalian cells.
P elements bearing ph-p regulatory sequences preferentially insert into regions containing known Pc and ph-p protein binding sites, perhaps because shared regulatory proteins bring transposons and insertion sites into close proximity.
Pc binds polytene chromosomes at 45 locations where other Pc-group proteins, encoded by the Psc and polyhomeotic genes, are present.
Distribution of the Pc protein in the bithorax complex was determined, and Pc protein quantitatively covers large regulatory regions of repressed genes.
The bithorax complex genes are regulated by the Pc group of genes, acting via 'Pc group response elements' (PREs), that can work even when removed from the normal bithorax complex context. The Pc group products apparently provide stable memory or imprinting of boundaries which are specified by gap and pair-rule regulators.
Pc and polyhomeotic proteins are constituents of a soluble multimeric nuclear protein complex.
When homozygous or hemizygous, Pc mutants are late embryonic lethals. Embryos with at least one dose of the BXC show incomplete head development and caudal transformations, the thoracic and first seven abdominal segments being partially transformed into the eighth abdominal segment (FBrf0032262; FBrf0063402; FBrf0039217; FBrf0039211). This homeotic effect in homozygotes is enhanced by increasing the dosage of the BXC. Transformations involve brain and ventral nerve cord as well as epidermis (FBrf0037316). Pc+ alleles in the mother weaken the homeotic effect (FBrf0063402; FBrf0038997). Pc2/Pc2 or Pc3/Pc3 clones induced in leg and eye-antennal tissue during larval development also show similar posteriorly-directed transformations (FBrf0037148; FBrf0063405). Pc/+ flies carrying at least one dose of the BXC show caudal transformations, i.e. partial conversion of wings into halteres and of anterior abdominal segments into more posterior ones. Some Pc heterozygotes show phenotypes characteristic of ANTC mutants, i.e. partial conversion of antennae into legs and of second and third legs into first legs (with sex combs in males) (FBrf0012037; FBrf0038059). The frequency of wing transformations varies directly with the BXC dosage, but does not seem to be changed by variation in ANTC dosage (FBrf0063405; FBrf0037909). The number of abdominal transformations, however, varies inversely with the doses of the BXC while it increases as the doses of the ANTC are increased (FBrf0038059; FBrf0063405). Other changes observed in Pc/+ flies include a transformation of ventral to dorsal wing (FBrf0051513; FBrf0039451), elevated, divergent, or crinkled wings, terminal gaps in the L4 wing vein, bent humeral or notopleural bristles, and defective sternopleural bristles, all abnormalities being less extreme in males than in females (sometimes absent in males). When doubly heterozygous with AntpYu and AntpB, Pc enhances Antp. The expression of all Pc mutant heterozygotes (including deficiencies for the locus) is enhanced by the second chromosome dominant, E(Pc) (FBrf0039451; FBrf0040741). Pc3/Pc3/Dp(1;3;4)7 flies (carrying a Pc+ duplication) show stronger leg and wing transformations than E(Pc)/+; Pc3/+ flies (FBrf0063405; FBrf0039451).
Pc+ may be considered a negative regulator of the bithorax complex (BXC) and the Antennapedia complex (ANTC), with a decreasing gradient of activity from anterior to posterior.
The chromo domain is a homologous protein motif between Pc and Su(var)205. Transgenic lines and transient assays in culture cells have been used to determine the functional role of the Pc chromo domain, it is important for the function of Pc and is absolutely required for binding of Pc protein to chromatin. The chromo domain could be involved in a packaging mechanism essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes.
Embryos mutant for two or more Pc group genes (Pc, Scm, Pcl, Psc, Asx, E(Pc), E(z), ph-d, pho and esc) show strong ectopic en expression, but only weak derepression occurs if embryo is mutant at only one of the Pc group genes. This effect is independent of the function of en itself, and wg.
Mutations of genes in the polycomb group (esc, E(z), Pc, ph-p, ph-d, Scm, Pcl, Sce, Asx, Psc, pho and Antp) cause abnormal segmental development due to the ectopic expression of abd-A and Abd-B. Embryos lacking both maternal and zygotic Pc product were generated to determine abd-A and Abd-B expression patterns.
Pc dominant loss-of-function mutants cause widespread alterations in cell fates by derepressing genes in the BXC and ANTC.
The Pc group genes are negative regulators of homeotic genes.
Mutations in maternal class gene Pc do not interact with RpII140wimp.
Homeotic gene activity programs primordia as either discs or histoblast nests by the early extended germ band stage. In Pc- embryos homeotic gene expression is no longer restricted to the normal expression domains.
The Pc gene product regulates Antp transcription directly at the chromosomal level. Regulation of Antp P2 differs from Antp P1 in that in that it can be repressed by transacting factors other than Pc.
The role of Pc in maintaining stable patterns of homeotic gene transcription has been studied.
Interactions with a mutation of the Pc gene were used to confirm that ash1 and ash2 are members of a functionally related class of genes whose alleles have similar transformation properties to mutations of trx. The dominant extra sex combs phenotype of adult males heterozygous for Pc mutations is sensitive to the gene dosage of trx, and is suppressed by heterozygosity for a trx deletion and enhanced by heterozygosity for a trx duplication.
Cell clones deficient for Pc and the BXC genes have abnormal wings and legs, Scr and en are derepressed in the absence of Pc and BXC function. By using the Pc- mutation and various BXC mutant combinations imaginal cell clones possessing different combinations of active homeotic genes have been generated. In the absence of BXC genes Pc- clones develop prothoracic patterns: Scr activity overrules Antp. Adding contributions of Ubx, abd-A and Abd-B results in thoracic or abdominal patterns.
Mutations in 18 complementation groups identify modifiers of Pc and/or Antp phenotypes. All 18 complementation groups are required for viability. Alleles of Pc, Pcl, Scm, Dll, brm, kto, Scr and trx show clear dominant enhancement or suppression of AntpScx, whereas alleles of vtd, Vha55, Su(Pc)37D, urd, mor, skd and osa do not.
Mutants of Pc exhibit a reduction in sex comb teeth on the second and third legs.
Genetic analysis of the Pc locus suggests it is a complex gene. Insufficiency of Pc products can be corrected by insufficiency of hb products or be exaggerated by the excess of the same products. Pc+ products regulate the expression Of the Ubx protein coding region.
The effect of various mutations in the bithorax and antennapedia complexes on the Pc mutant phenotype has been studied.
Pc mutants display homeotic transformation of head and thoracic segments towards A8.
Mutant males display sex combs in the second and third legs.