The histone methyltransferases Trithorax and Ash1 prevent transcriptional silencing by Polycomb group proteins

Klymenko, Tetyana; Müller, Jürg

doi:10.1038/sj.embor.7400111

Cited by 246 publications

(233 citation statements)

References 30 publications

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“…This suggests the presence of a default mechanism that represses FLC transcription in the absence of H3K4me3 marks. A similar mechanism was described in Drosophila, where the trxG proteins ASH1 and TRX have been proposed to counteract PcG repression, either by histone binding and/or H3K4-trimethylation, which subsequently prevents the binding of PcG proteins to HOX genes (Klymenko and Mü ller, 2004). The simultaneous binding of TRX and PcG proteins at the Ubx locus challenged this hypothesis (Papp and Mü ller, 2006).…”

Section: Flc Is Regulated Through Dosage-dependent Interactions Of Acmentioning

confidence: 90%

ARABIDOPSIS TRITHORAX1 Dynamically RegulatesFLOWERING LOCUS CActivation via Histone 3 Lysine 4 Trimethylation

et al. 2008

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Trithorax function is essential for epigenetic maintenance of gene expression in animals, but little is known about trithorax homologs in plants. ARABIDOPSIS TRITHORAX1 (ATX1) was shown to be required for the expression of homeotic genes involved in flower organogenesis. Here, we report a novel function of ATX1, namely, the epigenetic regulation of the floral repressor FLOWERING LOCUS C (FLC). Downregulation of FLC accelerates the transition from vegetative to reproductive development in Arabidopsis thaliana. In the atx1 mutant, FLC levels are reduced and the FLC chromatin is depleted of trimethylated, but not dimethylated, histone 3 lysine 4, suggesting a specific trimethylation function of ATX1. In addition, we found that ATX1 directly binds the active FLC locus before flowering and that this interaction is released upon the transition to flowering. This dynamic process stands in contrast with the stable maintenance of homeotic gene expression mediated by trithorax group proteins in animals but resembles the dynamics of plant Polycomb group function.

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Section: Flc Is Regulated Through Dosage-dependent Interactions Of Acmentioning

confidence: 90%

ARABIDOPSIS TRITHORAX1 Dynamically RegulatesFLOWERING LOCUS CActivation via Histone 3 Lysine 4 Trimethylation

et al. 2008

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“…The Ash1-specific methylation imprint was found to displace HP1 and PcG proteins, which are normally bound to repressed genes, and instead facilitates the binding of the Brahma chromatin remodeling complex (Beisel et al 2002). Interestingly, recent data from Drosophila studies indicate that TrxG proteins such as Trx and Ash1, rather than being general transcriptional coactivators, specifically function to prevent inappropriate silencing mediated by the PcG of transcriptional repressors (Klymenko and Muller 2004).…”

Section: Setting Trithorax Imprintsmentioning

confidence: 99%

Epigenetics and cancer

Lund¹,

Lohuizen²

2004

Genes Dev.

442

318

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Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development. This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.Epigenetic programming is crucial in mammalian development, and stable inheritance of epigenetic settings is essential for the maintenance of tissue-and cell-typespecific functions (Li 2002). With the exception of controlled genomic rearrangements, such as those of the immunoglobulin and T-cell receptor genes in B and T cells, all other differentiation processes are initiated or maintained through epigenetic processes. Not surprisingly therefore, epigenetic gene regulation is characterized overall by a high degree of integrity and stability. Evidence is accumulating that suggests that the intrinsic stability is caused by multiple interlocking feedback mechanisms between functionally unrelated epigenetic layers, such as DNA methyltransferases (DNMTs) and histone modifying enzymes, resulting in the stable commitment of a locus to a particular activity state. In somatic cells, the transcriptional status of most genes is epigenetically fixed. However, other genes, such as cell cycle checkpoint genes and genes directly affected by exogenous stimuli such as growth factors or cell-cell contact, likely reside in a balanced state sensitive to dynamic adjustments in histone modifications, thereby allowing for rapid responses to specific stimuli. Perturbation of epigenetic balances may lead to alterations in gene expression, ultimately resulting in cellular transformation and malignant outgrowth; the involvement of deregulated epigenetic mechanisms in cancer development has received increased attention in recent years.Per definition, epigenetic regulators alter the activities and abilities of a cell without directly affecting and mutating the sequence of the DNA. In this review, we deal with epigenetic gene regulation as imposed by DNA methylation, covalent modifications of the canonical core histones, deposition of variant histone proteins, local nucleosome remodeling, and long-range epigenetic regulators. Understanding the molecular details behind "epigenetic cancer diseases" holds potentially important prospects for medical treatment, as it allows for novel strategies for drug development. A number of recent reviews have provided details on epigenetic mechanisms and their involvement in cancer, and we refer to these for more in-depth information on individual epigenetic mechanisms

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“…D. melanogaster trxG proteins were identified as suppressors of PcG mutations that cause trimethylation of histone 3 Lys-4 (H3K4me3) and activate gene expression (Poux et al, 2002;Klymenko and Müller, 2004;Schwartz and Pirrotta, 2007). Subtle regulation of histone methylation homeostasis by PcG and trxG on target genes determines gene expression status; however, the molecular mechanisms that translate histone modification patterns to specific transcriptional states remain unclear (Poux et al, 2002;Klymenko and Müller, 2004).…”

mentioning

confidence: 99%

“…The two D. melanogaster PcG protein complexes, Polycomb Repressive Complex1 (PRC1) and PRC2, the components of which are highly conserved among eukaryotic organisms, cooperate to maintain silencing through trimethylation of histone 3 Lys-27 (H3K27me3) of their target genes (Schwartz and Pirrotta, 2007). D. melanogaster trxG proteins were identified as suppressors of PcG mutations that cause trimethylation of histone 3 Lys-4 (H3K4me3) and activate gene expression (Poux et al, 2002;Klymenko and Müller, 2004;Schwartz and Pirrotta, 2007). Subtle regulation of histone methylation homeostasis by PcG and trxG on target genes determines gene expression status; however, the molecular mechanisms that translate histone modification patterns to specific transcriptional states remain unclear (Poux et al, 2002;Klymenko and Müller, 2004).…”

mentioning

confidence: 99%

EMBRYONIC FLOWER1 and ULTRAPETALA1 Act Antagonistically on Arabidopsis Development and Stress Response

Liu

Kim

et al. 2013

Plant Physiology

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Epigenetic regulation of gene expression is of fundamental importance for eukaryotic development. EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene that participates in Polycomb group-mediated transcriptional repression of target genes such as the flower MADS box genes AGAMOUS, APETALA3, and PISTILLATA. Here, we investigated the molecular mechanism underlying the curly leaf and early flowering phenotypes caused by reducing EMF1 activity in the leaf primordia of LFYasEMF1 transgenic plants and propose a combined effect of multiple flower MADS box gene activities on these phenotypes. ULTRAPETALA1 (ULT1) functions as a trithorax group factor that counteracts Polycomb group action in Arabidopsis (Arabidopsis thaliana). Removing ULT1 activity rescues both the abnormal developmental phenotypes and most of the misregulated gene expression of LFYasEMF1 plants. Reducing EMF1 activity increases salt tolerance, an effect that is diminished by introducing the ult1-3 mutation into the LFYasEMF1 background. EMF1 is required for trimethylating lysine-27 on histone 3 (H3K27me3), and ULT1 associates with ARABIDOPSIS TRITHORAX1 (ATX1) for trimethylating lysine-3 on histone 4 (H3K4me3) at flower MADS box gene loci. Reducing EMF1 activity decreases H3K27me3 marks and increases H3K4me3 marks on target gene loci. Removing ULT1 activity has the opposite effect on the two histone marks. Removing both gene activities restores the active and repressive marks to near wild-type levels. Thus, ULT1 acts as an antirepressor that counteracts EMF1 action through modulation of histone marks on target genes. Our analysis indicates that, instead of acting as off and on switches, EMF1 and ULT1 mediate histone mark deposition and modulate transcriptional activities of the target genes.

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The histone methyltransferases Trithorax and Ash1 prevent transcriptional silencing by Polycomb group proteins

Cited by 246 publications

References 30 publications

ARABIDOPSIS TRITHORAX1 Dynamically RegulatesFLOWERING LOCUS CActivation via Histone 3 Lysine 4 Trimethylation

ARABIDOPSIS TRITHORAX1 Dynamically RegulatesFLOWERING LOCUS CActivation via Histone 3 Lysine 4 Trimethylation

Epigenetics and cancer

EMBRYONIC FLOWER1 and ULTRAPETALA1 Act Antagonistically on Arabidopsis Development and Stress Response

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