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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/Trithorax response elements (PRE/TREs) maintain transcriptional decisions to ensure correct cell identity during development and differentiation. There are thought to be over 100 PRE/TREs in the Drosophila genome, but only very few have been identified due to the lack of a defining consensus sequence. Here we report the definition of sequence criteria that distinguish PRE/TREs from non-PRE/TREs. Using this approach for genome-wide PRE/TRE prediction, we identify 167 candidate PRE/TREs, which map to genes involved in development and cell proliferation. We show that candidate PRE/TREs are bound and regulated by Polycomb proteins in vivo, thus demonstrating the validity of PRE/TRE prediction. Using the larger data set thus generated, we identify three sequence motifs that are conserved in PRE/TRE sequences.
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PMID:Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster. 1460 76

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

Polycomb/Trithorax group response elements (PRE/TREs) are fascinating chromosomal pieces. Just a few hundred base pairs long, these elements can remember and maintain the active or silent transcriptional state of their associated genes for many cell generations, long after the initial determining activators and repressors have disappeared. Recently, substantial progress has been made towards understanding the nuts and bolts of PRE/TRE function at the molecular level and in experimentally mapping PRE/TRE sites across whole genomes. Here we examine the insights, controversies and new questions that have been generated by this recent flood of data.
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PMID:Polycomb/Trithorax response elements and epigenetic memory of cell identity. 1718 23

We analysed the nuclear organization of the Polycomb/Trithorax group response element (PRE/TRE) Fab-7 and of other PRE/TREs in larval tissues of D. melanogaster. The results show that pairing/clustering of transgenic and endogenous Fab-7 elements and of other endogenous PRE/TREs occurs only to a limited degree in a highly locus-specific and tissue-specific manner. However, transgenic Fab-7 elements as well as the Fab-7-regulated Abd-B gene and other endogenous loci preferentially occupied defined nuclear regions. Preferred association with the nuclear periphery was observed in the inactive state. However, also in the active state, Fab-7 was often found associated with the nuclear periphery as well as with the boundary of heterochromatin in a fly line- and tissue-specific manner. The boundary between heterochromatin and euchromatin revealed a highly complex architecture in the three-dimensional nuclear space with a close juxtaposition of active and repressed domains. The results suggest that such complex architectures create nuclear microenvironments sustaining specific states of activity of defined PRE/TREs. However, the data also show that the positional behaviour of the transgenic Fab-7 element does not apply to PRE/TREs in general. Altogether, this finding and the highly locus-, tissue-, and fly line-specific behaviour with regard to nuclear positioning and pairing/clustering suggest that the relationships between nuclear organization and functional regulation of PRE/TREs are highly complex and that simple models making general predictions might not be appropriate.
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PMID:The nuclear organization of Polycomb/Trithorax group response elements in larval tissues of Drosophila melanogaster. 1856 Sep 94

Myostatin (MSTN) is a member of the transforming growth factor-beta superfamily that functions as a negative regulator of skeletal muscle development and growth in mammals. Although several MSTN promoters were described in fish, no functional analysis was reported so far. Here, the 5' flanking region (1372 bp) of the MSTN-1 gene of the marine fish Sparus aurata (saMSTN-1) was cloned, sequenced and characterized. It contains two consensus sequences for TATA box (TATAA), a CAAT box, ten putative E-boxes known as binding sites to myogenic basic helix-loop-helix transcription factors (TFs) and two putative binding sites to TF Myocyte enhancing factor-2 (MEF2). In addition, it has several putative binding sites to TF Pit-1a and several response elements to nuclear receptors (GRE, ERE, PRE, ARE, TRE, RARE and PPARRE) and cAMP-response elements. Transcriptional activity of five genomic fragments (truncated at their upstream region) of 372, 941, 972, 1113 and 1355 bp was studied in vitro, using transient transfection in A204 cells. All constructs directed luciferase activity, with the highest activity obtained by the 1113 bp fragment. These experiments show that all five genomic fragments are functional MSTN promoters and differences in promoter activity might be due to presence of enhancers and/or repressor sequences, regulating MSTN promoter activity.
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PMID:Characterization and functional analysis of the 5' flanking region of Sparus aurata myostatin-1 gene. 1893 Jan 59

Transgenerational epigenetic inheritance, while poorly understood, is of great interest because it might help explain the increase in the incidence of diseases with an environmental contribution in humans, such as cancer, diabetes, and heart disease. Here, we review five Drosophila examples of transgenerational epigenetic inheritance and propose a unified mechanism that involves Polycomb Response Element/Trithorax Response Element (PRE/TRE) occupancy by either Polycomb Group (PcG) protein complexes or Trithorax group (TrxG) complexes. Among their other activities, PcG complexes cause histone 3 lysine 27 tri-methylation associated with repressed chromatin, whereas Trithorax group (TrxG) complexes induce histone 3 lysine 4 tri-methylation associated with actively transcribed chromatin. In this model, Hsp90 is an environmentally sensitive chromatin remodeling regulator that causes a switch in the chromatin from a permissive state to a non-permissive state for transcription. Consistent with this model, Hsp90 has recently been shown to be a chaperone for Tah1p (TPR-containing protein associated with Hsp90) and Pih1p (protein interacting with Hsp90), which connect to the chromatin remodelling factor Rvb1p (RuvB-like protein 1)/Rvb2p in yeast [1]. Also, Hsp90 is required for optimal activity of the histone H3 lysine-4 methyltransferase SMYD3 in mammals [2, 3]. Since PcG and TrxG complexes are involved in the post-translational modifications of histones, and since such modifications have been shown to be required to maintain imprinted marks, this unified mechanism might also help to explain transgenerational epigenetic inheritance in humans.
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PMID:Hsp90 affecting chromatin remodeling might explain transgenerational epigenetic inheritance in Drosophila. 1950 39

Forum domains are stretches of chromosomal DNA that are excised from eukaryotic chromosomes during their spontaneous non-random fragmentation. Most forum domains are 50-200 kb in length. We mapped forum domain termini using FISH on polytene chromosomes and we performed genome-wide mapping using a Drosophila melanogaster genomic tiling microarray consisting of overlapping 3 kb fragments. We found that forum termini very often correspond to regions of intercalary heterochromatin and regions of late replication in polytene chromosomes. We found that forum domains contain clusters of several or many genes. The largest forum domains correspond to the main clusters of homeotic genes inside BX-C and ANTP-C, cluster of histone genes and clusters of piRNAs. PRE/TRE and transcription factor binding sites often reside inside domains and do not overlap with forum domain termini. We also found that about 20% of forum domain termini correspond to small chromosomal regions where Ago1, Ago2, small RNAs and repressive chromatin structures are detected. Our results indicate that forum domains correspond to big multi-gene chromosomal units, some of which could be coordinately expressed. The data on the global mapping of forum domains revealed a strong correlation between fragmentation sites in chromosomes, particular sets of mobile elements and regions of intercalary heterochromatin.
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PMID:Genome-wide profiling of forum domains in Drosophila melanogaster. 2124 82


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