Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression

Saint Louis University School of Medicine and the Saint Louis University Cancer Center, St. Louis, Missouri 63104, USA.
Annual Review of Biochemistry (Impact Factor: 26.53). 02/2006; 75(1):243-69. DOI: 10.1146/annurev.biochem.75.103004.142422
Source: PubMed

ABSTRACT It is more evident now than ever that nucleosomes can transmit epigenetic information from one cell generation to the next. It has been demonstrated during the past decade that the posttranslational modifications of histone proteins within the chromosome impact chromatin structure, gene transcription, and epigenetic information. Multiple modifications decorate each histone tail within the nucleosome, including some amino acids that can be modified in several different ways. Covalent modifications of histone tails known thus far include acetylation, phosphorylation, sumoylation, ubiquitination, and methylation. A large body of experimental evidence compiled during the past several years has demonstrated the impact of histone acetylation on transcriptional control. Although histone modification by methylation and ubiquitination was discovered long ago, it was only recently that functional roles for these modifications in transcriptional regulation began to surface. Highlighted in this review are the recent biochemical, molecular, cellular, and physiological functions of histone methylation and ubiquitination involved in the regulation of gene expression as determined by a combination of enzymological, structural, and genetic methodologies.

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    • "H2Bub1 can modulate chromatin structure and DNA accessibility to regulate diverse DNA-dependent processes such as gene transcription (Zhang, 2003; Shilatifard, 2006; Pinder et al., 2013). RNA interference against human RNF20/RNF40 leads to reduced H2Bub1 and subsequent repression of HOX gene expression (Zhu et al., 2005). "
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    ABSTRACT: Histone H2B monoubiquitination (H2Bub1) is an important regulatory mechanism in eukaryotic gene transcription and is essential for normal plant development. However, the function of H2Bub1 in reproductive development remains elusive. Here, we report OsHUB1 (Oryza sativa HISTONE MONO-UBIQUITINATION1) and OsHUB2, the homologues of Arabidopsis HUB1 and HUB2 proteins which function as E3 ligases in H2Bub1, are involved in late anther development in rice. oshub mutants exhibit abnormal tapetum development and aborted pollen in postmeiotic anthers. Knock-out of OsHUB1 or OsHUB2 results in the loss of H2Bub1, and a reduction in the levels of dimethylated lysine 4 on histone 3 (H3K4me2). Anther transcriptome analysis revealed that several key tapetum degradation-related genes including OsC4, OsCP1 and UDT1 were down-regulated in the mutants. Further, chromatin immunoprecipitation assays demonstrate that H2Bub1 directly targets OsC4, OsCP1 and UDT1 genes and enrichment of H2Bub1 and H3K4me2 in the targets is consistent to some degree. Our studies suggest that histone H2B monoubiquitination, mediated by OsHUB1 and OsHUB2, is an important epigenetic modification that in concert with H3K4me2 modulates transcriptional regulation of anther development in rice. Copyright © 2015, American Society of Plant Biologists.
    Plant physiology 07/2015; DOI:10.1104/pp.114.256578 · 7.39 Impact Factor
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    • "Comparing H3K36me3 ChIP-seq and mRNA-seq results revealed an absence of H3K36me3 on undetectably and weakly expressed genes (log 10 FPKM <0) (Supplemental Fig. S1E), consistent with previous findings that H3K36me3 marks actively transcribed genes (Shilatifard 2006; Kouzarides 2007). For genes that are actively expressed at moderate levels (log 10 FPKM between 0 and 1), their mRNA levels positively correlated with their gene body H3K36me3 marking (Spearman's correlation , ρ = 0.17, 0.13, and 0.14; P-value < 0.001) (Supplemental Fig. S1E). "
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    ABSTRACT: Functional data indicate that specific histone modification enzymes can be key to longevity in Caenorhabditis elegans, but the molecular basis of how chromatin structure modulates longevity is not well understood. In this study, we profiled the genome-wide pattern of trimethylation of Lys36 on histone 3 (H3K36me3) in the somatic cells of young and old Caenorhabditis elegans. We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequences on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene bodies irrespective of their corresponding mRNA abundance. Interestingly, 3' untranslated region (UTR) length strongly correlates with H3K36me3 levels and age-dependent mRNA expression stability. A similar negative correlation between H3K36me3 marking and mRNA expression change during aging was also observed in Drosophila melanogaster, suggesting a conserved mechanism for H3K36me3 in suppressing age-dependent mRNA expression change. Importantly, inactivation of the methyltransferase met-1 resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened life span, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity. © 2015 Pu et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & development 04/2015; 29(7):718-31. DOI:10.1101/gad.254144.114 · 12.64 Impact Factor
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    • "Euchromatin in the yeast Saccharomyces cerevisiae is characterized by Dot1-mediated H3K79 trimethylation (H3K79me3) (Briggs et al. 2002; van Leeuwen et al. 2002; Henry et al. 2003; Wood et al. 2003; Kao et al. 2004; Xiao et al. 2005; Pavri et al. 2006; Shilatifard 2006). H3K79me3, a mark closely associated with active transcription , is typically present in the coding regions of genes but absent from intergenic regions as well as subtelomeric heterochromatin (Ng et al. 2003; Pokholok et al. 2005), both of which are transcriptionally silent. "
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    ABSTRACT: Here we show that the Ino80 chromatin remodeling complex (Ino80C) directly prevents euchromatin from invading transcriptionally silent chromatin within intergenic regions and at the border of euchromatin and heterochromatin. Deletion of Ino80C subunits leads to increased H3K79 methylation and noncoding RNA polymerase II (Pol II) transcription centered at the Ino80C-binding sites. The effect of Ino80C is direct, as it blocks H3K79 methylation by Dot1 in vitro. Heterochromatin stimulates the binding of Ino80C in vitro and in vivo. Our data reveal that Ino80C serves as a general silencing complex that restricts transcription to gene units in euchromatin. © 2015 Xue et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & Development 02/2015; 29(4):350-5. DOI:10.1101/gad.256255.114 · 12.64 Impact Factor
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