Trithorax Group Complexes Research Articles

Rice Trithorax factor ULTRAPETALA 1 (OsULT1) specifically binds to “GAGAG” sequence motif present in Polycomb response elements

Co-ordinated interplay between Polycomb group (PcG) and Trithorax group (TrxG) of proteins regulate chromatin state and maintain the transcription “off” and “on” state of a gene in higher eukaryotes. Targeting PcG complex to a specific locus is mediated by DNA sequences known as Polycomb response elements. Interestingly, these PREs are also recognized by TrxG proteins to antagonise PcG mediated gene repression. In this study, we have characterised DNA binding property of rice trithorax group factor ULTRAPETALA1 (OsULT1) which has a SAND domain and B–box motif. Chromatin immunoprecipitation assay indicates cold induced enrichment of OsULT1 occupancy and a decrease in H3K27me3 mark in the promoter region of OsDREB1b gene, during transcription activation. OsULT1 binds to the cis motif “GAGAG”, and the sequence specificity is contributed mainly by the SAND domain. GAGAG is one of the cis motifs present in PREs that are recognized by Drosophila GAGA factor and Pipsqueak. Thus, binding of OsULT1 to GAGAG motif, along with a decrease in H3K27me3 suggests that OsULT1 antagonises the repressive effect of PcG complex for transcriptional activation of OsDREB1b. Moreover, OsULT1 interacts with rice SET domain-containing methyltransferase TRX1, suggesting OsULT1 is an integral part of plant Trithorax group complex. Furthermore, the increase in ULT1 levels during environmental cues suggests its involvement in the transcriptional regulation of stress responsive genes. Collectively, these results suggest that the antagonistic functions of PcG and TrxG proteins and the mechanism of recruitment of these complexes to target loci are evolutionarily conserved for gene expression regulation across kingdoms.

Deregulated Polycomb functions in myeloproliferative neoplasms.

Polycomb proteins function in the maintenance of gene silencing via post-translational modifications of histones and chromatin compaction. Genetic and biochemical studies have revealed that the repressive function of Polycomb repressive complexes (PRCs) in transcription is counteracted by the activating function of Trithorax-group complexes; this balance fine-tunes the expression of genes critical for development and tissue homeostasis. The function of PRCs is frequently dysregulated in various cancer cells due to altered expression or recurrent somatic mutations in PRC genes. The tumor suppressive functions of EZH2-containing PRC2 and a PRC2-related protein ASXL1 have been investigated extensively in the pathogenesis of hematological malignancies, including myeloproliferative neoplasms (MPN). BCOR, a component of non-canonical PRC1, suppresses various hematological malignancies including MPN. In this review, we focus on recent findings on the role of PRCs in the pathogenesis of MPN and the therapeutic impact of targeting the pathological functions of PRCs in MPN.

Dynamics of H3K4me3 Chromatin Marks Prevails over H3K27me3 for Gene Regulation during Flower Morphogenesis in Arabidopsis thaliana

Plant life-long organogenesis involves sequential, time and tissue specific expression of developmental genes. This requires activities of Polycomb Group (PcG) and trithorax Group complexes (trxG), respectively responsible for repressive Histone 3 trimethylation at lysine 27 (H3K27me3) and activation-related Histone 3 trimethylation at lysine 4 (H3K4me3). However, the genome-wide dynamics in histone modifications that occur during developmental processes have remained elusive. Here, we report the distributions of H3K27me3 and H3K4me3 along with expression changes, in a developmental series including Arabidopsis thaliana leaf and three stages of flower development. We found that chromatin mark levels are highly dynamic over the time series on nearly half of all Arabidopsis genes. Moreover, during early flower morphogenesis, changes in H3K4me3 prevail over changes in H3K27me3 and quantitatively correlate with expression changes, while H3K27me3 changes occur later. Notably, we found that H3K4me3 increase during the early activation of PcG target genes while H3K27me3 level remain relatively constant at the locus. Our results reveal that H3K4me3 predicts changes in gene expression better than H3K27me3, unveil unexpected chromatin mechanisms at gene activation and underline the relevance of tissue-specific temporal epigenomics.

Sensing cellular states--signaling to chromatin pathways targeting Polycomb and Trithorax group function.

Cells respond to extra- and intra-cellular signals by dynamically changing their gene expression patterns. After termination of the original signal, new expression patterns are maintained by epigenetic DNA and histone modifications. This represents a powerful mechanism that enables long-term phenotypic adaptation to transient signals. Adaptation of epigenetic landscapes is important for mediating cellular differentiation during development and allows adjustment to altered environmental conditions throughout life. Work over the last decade has begun to elucidate the way that extra- and intra-cellular signals lead to changes in gene expression patterns by directly modulating the function of chromatin-associated proteins. Here, we review key signaling-to-chromatin pathways that are specifically thought to target Polycomb and Trithorax group complexes, a classic example of epigenetically acting gene silencers and activators important in development, stem cell differentiation and cancer. We discuss the influence that signals triggered by kinase cascades, metabolic fluctuations and cell-cycle dynamics have on the function of these protein complexes. Further investigation into these pathways will be important for understanding the mechanisms that maintain epigenetic stability and those that promote epigenetic plasticity.

A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3.

Histone methylation has emerged as an important mechanism for regulating the transcriptional accessibility of chromatin. Several methyltransferases have been shown to target histone amino-terminal tails and mark nucleosomes associated with either euchromatic or heterochromatic states. However, the biochemical machinery responsible for regulating histone methylation and integrating it with other cellular events has not been well characterized. We report here the purification, molecular identification, and genetic and biochemical characterization of the Set1 protein complex that is necessary for methylation of histone H3 at lysine residue 4 in Saccharomyces cerevisiae. The seven-member 363-kDa complex contains homologs of Drosophila melanogaster proteins Ash2 and Trithorax and Caenorhabditis elegans protein DPY-30, which are implicated in the maintenance of Hox gene expression and regulation of X chromosome dosage compensation, respectively. Mutations of Set1 protein comparable to those that disrupt developmental function of its Drosophila homolog Trithorax abrogate histone methylation in yeast. These studies suggest that epigenetic regulation of developmental and sex-specific gene expression are species-specific readouts for a common chromatin remodeling machinery associated mechanistically with histone methylation.