Gene/Protein Disease Symptom Drug Enzyme Compound
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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 yeast, Rad7 and Rad16 are two proteins required for nucleotide excision repair (NER) of non-transcribed chromatin. They have roles in damage recognition, in the postincision steps of NER, and in ultraviolet-light-dependent histone H3 acetylation. Moreover, Rad16 is an ATP-ase of the SNF2 superfamily and therefore might facilitate chromatin repair by nucleosome remodelling. Here, we used yeast rad7 Delta rad16 Delta mutants and show that Rad7-Rad16 is also required for NER of UV-lesions in three functionally distinct nucleosome-free regions (NFRs), the promoter and 3'-end of the URA3 gene and the ARS1 origin of replication. Moreover, rapid repair of UV-lesions by photolyase confirmed that nucleosomes were absent and that neither UV-damage formation nor rad7 Delta rad16 Delta mutations altered chromatin accessibility in NFRs. The data are consistent with a role of Rad7-Rad16 in damage recognition and processing in absence of nucleosomes. An additional role in nucleosome remodelling is discussed.
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PMID:Functionally distinct nucleosome-free regions in yeast require Rad7 and Rad16 for nucleotide excision repair. 1832 64

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

Histone H3 mutations in residues that cluster in a discrete region on the nucleosome surface around lysine 79 of H3 affect H3-K79 methylation, impair transcriptional silencing in subtelomeric chromatin, and reveal distinct contributions of histone H3 to various DNA-damage response and repair pathways. These residues might act by recruitment of silencing and DNA-damage response factors. Alternatively, their location on the nucleosome surface suggests a possible involvement in nucleosome positioning, stability and nucleosome interactions. Here, we show that the yeast H3 mutants hht2-T80A, hht2-K79E, hht2-L70S, and hht2-E73D show normal nucleosome positioning and stability in minichromosomes. However, loss of silencing in a subtelomeric URA3 gene correlates with a shift of the promoter nucleosome, while nucleosome positions and stability in the coding region are maintained. Moreover, the H3 mutants show normal repair of UV lesions by photolyase and nucleotide excision repair in minichromosomes and slightly enhanced repair in the subtelomeric region. Thus, these results support a role of those residues in the recruitment of silencing proteins and argue against a general role in nucleosome organization.
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PMID:Contributions of histone H3 nucleosome core surface mutations to chromatin structures, silencing and DNA repair. 2205 85

The transition to flowering in winter wheat requires prolonged exposure to low temperature, a process called vernalization. This process is regulated by a genetic pathway that involves at least three genes, Triticum aestivum VERNALIZATION 1 (TaVRN1), Triticum aestivum VERNALIZATION 2 (TaVRN2) and Triticum aestivum FLOWERING LOCUS T-like 1 (TaFT1). These genes regulate flowering by integrating environmental and developmental cues. To determine whether the expression of these genes is associated with the chromatin methylation state during vernalization in wheat, the level of two markers of histone modifications, the activator histone H3 trimethylation of lysine 4 (H3K4me3) and the repressor histone H3 trimethylation of lysine 27 (H3K27me3) were measured at the promoter regions of these three genes. Bioinformatics analysis of these promoters demonstrates the presence of conserved cis-acting elements in the promoters of the three vernalization genes, TaVRN1, TaVRN2 and TaFT1. These elements are targeted by common transcription factors in the vernalization responsive cereals. These promoters also contain the functional "units" PRE/TRE targeted by Polycomb and Trithorax proteins that maintain repressed or active transcription states of developmentally regulated genes. These proteins are known to be associated with the regulation of H3K4me3 and H3K27me3. Expression studies indicate that TaVRN1 and TaFT1 are up-regulated by vernalization in winter wheat. This up-regulation is associated with increased level of the activator H3K4me3 with no change in the level of the repressor H3K27me3 at the promoter region. This study shows that the flowering transition induced by vernalization in winter wheat is associated with histone methylation at the promoter level of TaVRN1 and TaFT1 while the role of these markers is less evident in TaVRN2 repression. This may represent part of the cellular memory of vernalization in wheat.
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PMID:Expression of vernalization responsive genes in wheat is associated with histone H3 trimethylation. 2268 14