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Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Drosophila, two classes of genes, the trithorax group and the Polycomb group, are required in concert to maintain gene expression by regulating chromatin structure. We have identified Trithorax protein (TRX) binding elements within the bithorax complex and have found that within the bxd/pbx regulatory region these elements are functionally relevant for normal expression patterns in embryos and confer TRX binding in vivo. TRX was localized to three closely situated sites within a 3-kb chromatin maintenance unit with a modular structure. Results of an in vivo analysis showed that these DNA fragments (each approximately 400 bp) contain both TRX- and Polycomb-group response elements (TREs and PREs) and that in the context of the endogenous Ultrabithorax gene, all of these elements are essential for proper maintenance of expression in embryos. Dissection of one of these maintenance modules showed that TRX- and Polycomb-group responsiveness is conferred by neighboring but separable DNA sequences, suggesting that independent protein complexes are formed at their respective response elements. Furthermore, we have found that the activity of this TRE requires a sequence (approximately 90 bp) which maps to within several tens of base pairs from the closest neighboring PRE and that the PRE activity in one of the elements may require a binding site for PHO, the protein product of the Polycomb-group gene pleiohomeotic. Our results show that long-range maintenance of Ultrabithorax expression requires a complex element composed of cooperating modules, each capable of interacting with both positive and negative chromatin regulators.
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PMID:Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences. 1037 68

The polyhomeotic (ph) gene is a member of the Polycomb group of genes (Pc-G), which are required for the maintenance of the spatial expression pattern of homeotic genes. In contrast to homeotic genes, ph is ubiquitously expressed and it is quantitatively regulated. ph is negatively regulated by the Pc-G genes, except Psc, and positively regulated by the antagonist trithorax group of genes (trx-G), suggesting that Pc-G and trx-G response elements (PREs and TREs) exist at the ph locus. In this study, we have functionally characterized PREs and TREs at the ph locus that function in transgenic constructs. We have identified a strong PRE and TRE in the ph proximal unit as well as a weak one in the ph distal unit. The PRE/TRE of both ph units appear atypical compared with the well-defined homeotic maintenance elements because the minimal ph proximal response element activity requires at least 2 kb of sequence and does not work at long range. We have used chromatin immunoprecipitation experiments on cultured cells and embryos to show that Pc-G proteins are located in restricted regions, close to the ph promoters that overlap functionally defined PRE/TREs. Our data suggest that ph PRE/TREs are cis-acting DNA elements that modulate rather than silence Pc-G- and trx-G-mediated regulation, enlarging the role of these two groups of genes in transcriptional regulation.
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PMID:Identification and characterization of polyhomeotic PREs and TREs. 1449 51

Polycomb and trithorax group (PcG and trxG) proteins maintain silent and active transcriptional states, respectively, throughout development. In Drosophila, PcG and trxG proteins associate with DNA regions named Polycomb and trithorax response elements (PRE and TRE), but the mechanisms of recruitment are unknown. We previously characterized a minimal element from the regulatory region of the Abdominal-B gene, termed Ab-Fab. Ab-Fab contains a PRE and a TRE and is able to maintain repressed or active chromatin states during development. Here we show that the Dorsal switch protein 1 (DSP1), a Drosophila HMGB2 homologue, binds to a sequence present within Ab-Fab and in other characterized PREs. Addition of this motif to an artificial sequence containing Pleiohomeotic and GAGA factor consensus sites is sufficient for PcG protein recruitment in vivo. Mutations that abolish DSP1 binding to Ab-Fab and to a PRE from the engrailed locus lead to loss of PcG protein binding, loss of silencing, and switching of these PREs into constitutive TREs. The binding of DSP1 to PREs is therefore important for the recruitment of PcG proteins.
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PMID:Recruitment of Drosophila Polycomb group proteins to chromatin by DSP1. 1579 Dec 60

The Polycomb gene was discovered 60 years ago as a mutation inducing a particular homeotic phenotype. Subsequent work showed that Polycomb is a general repressor of homeotic genes. Other genes with similar function were identified and named Polycomb group (PcG) genes, while trithorax group (trxG) genes were shown to counteract PcG-mediated repression of homeotic genes. We now know that PcG and trxG proteins are conserved factors that regulate hundreds of different genomic loci. A sophisticated pathway is responsible for recruitment of these proteins at regulatory regions that were named PcG and trxG response elements (PRE and TRE). Once recruited to their targets, multimeric PcG and trxG protein complexes regulate transcription by modulating chromatin structure, in particular via deposition of specific post-translational histone modification marks and control of chromatin accessibility, as well as regulation of the three-dimensional nuclear organization of PRE and TRE. Here, we recapitulate the history of PcG and trxG gene discovery, we review the current evidence on their molecular function and, based on this evidence, we propose a revised classification of genes involved in PcG and trxG regulatory pathways.
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PMID:From genetics to epigenetics: the tale of Polycomb group and trithorax group genes. 1682 Nov 33

Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins.
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PMID:Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome. 2380

The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines. The hPRE-PIK3C2B interacts with the members of multiple activating complexes (COMPASS-like). The increase in the interaction of MLL and MLL4 on depletion of YY1 and the increase in the enrichment of YY1 and EZH2 upon MLL knockdown at the hPRE-PIK3C2B indicate the dual occupancy and suggest a concentration dependent enrichment of the activator or the repressor complex at hPRE-PIK3C2B. Further, we show that the hPRE-PIK3C2B interacts with the Drosophila homologues of PcG and TrxG proteins in transgenic flies. Here, we found that there is an increased enrichment of Pc (Polycomb) in comparison to Trx (TrxG protein) at hPRE-PIK3C2B in the Drosophila transgenic flies and this seems to be the default state while the balance is tipped towards the trithorax complex in PcG mutants. To the best of our knowledge, this is one of the early demonstrations of human PRE acting as a TRE without any sequence alteration.
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PMID:Human PRE-PIK3C2B, an intronic cis-element with dual function of activation and repression. 2837 18