Diverse histone modifications on histone 3 lysine 9 and their relation to DNA methylation in specifying gene silencing

Jiejun Wu; Shu-Huei Wang; Potter, Dustin; Liu, Joseph C; Smith, Laura T; Yue-Zhong Wu; Huang, Tim H-M; Plass, Christoph
January 2007
BMC Genomics;2007, Vol. 8, p131
Academic Journal
Background: Previous studies of individual genes have shown that in a self-enforcing way, dimethylation at histone 3 lysine 9 (dimethyl-H3K9) and DNA methylation cooperate to maintain a repressive mode of inactive genes. Less clear is whether this cooperation is generalized in mammalian genomes, such as mouse genome. Here we use epigenomic tools to simultaneously interrogate chromatin modifications and DNA methylation in a mouse leukemia cell line, L1210. Results: Histone modifications on H3K9 and DNA methylation in L1210 were profiled by both global CpG island array and custom mouse promoter array analysis. We used chromatin immunoprecipitation microarray (ChIP-chip) to examine acetyl-H3K9 and dimethyl-H3K9. We found that the relative level of acetyl-H3K9 at different chromatin positions has a wider range of distribution than that of dimethyl-H3K9. We then used differential methylation hybridization (DMH) and the restriction landmark genome scanning (RLGS) to analyze the DNA methylation status of the same targets investigated by ChIP-chip. The results of epigenomic profiling, which have been independently confirmed for individual loci, show an inverse relationship between DNA methylation and histone acetylation in regulating gene silencing. In contrast to the previous notion, dimethyl-H3K9 seems to be less distinct in specifying silencing for the genes tested. Conclusion: This study demonstrates in L1210 leukemia cells a diverse relationship between histone modifications and DNA methylation in the maintenance of gene silencing. Acetyl-H3K9 shows an inverse relationship between DNA methylation and histone acetylation in regulating gene silencing as expected. However, dimethyl-H3K9 seems to be less distinct in relation to promoter methylation. Meanwhile, a combination of epigenomic tools is of help in understanding the heterogeneity of epigenetic regulation, which may further our vision accumulated from single-gene studies.


Related Articles

  • Euchromatin islands in large heterochromatin domains are enriched for CTCF binding and differentially DNA-methylated regions. Wen, Bo; Wu, Hao; Loh, Yuin-Han; Briem, Eirikur; Daley, George Q.; Feinberg, Andrew P. // BMC Genomics;2012, Vol. 13 Issue 1, p566 

    Background: The organization of higher order chromatin is an emerging epigenetic mechanism for understanding development and disease. We and others have previously observed dynamic changes during differentiation and oncogenesis in large heterochromatin domains such as Large Organized Chromatin K...

  • Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients. Li Zhang; Keli Zhong; Yong Dai; Hanxin Zhou // Journal of Gastroenterology;2009, Vol. 44 Issue 4, p305 

    Trimethylation of histone H3 lysine 27 (H3K27me3) is a posttranslational modification that is highly correlated with genomic silencing. In gastric cancer (GC), global and gene-specific DNA methylation changes have been demonstrated to occur. However, to date, our understanding of the alterations...

  • Structure of the SET domain histone lysine methyltransferase Clr4. Min, Jinrong; Zhang, Xing; Cheng, Xiaodong; Grewal, Shiv I.S.; Xu, Rui-Ming // Nature Structural Biology;Nov2002, Vol. 9 Issue 11, p828 

    Methylation of histone H3 lysine 9 is an important component of the 'histone code' for heterochromatic gene silencing. The SET domain-containing Clr4 protein, a close relative of Su(var)3-9 proteins in higher eukaryotes, specifically methylates lysine 9 of histone H3 and is essential for...

  • Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states. Frederiks, Floor; Tzouros, Manuel; Oudgenoeg, Gideon; van Welsem, Tibor; Fornerod, Maarten; Krijgsveld, Jeroen; van Leeuwen, Fred // Nature Structural & Molecular Biology;Jun2008, Vol. 15 Issue 6, p550 

    Whereas mono-, di- and trimethylation states of lysines on histones typically have specific functions, no specific functions have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1. Here we show that Dot1, in contrast to other known...

  • Study of methylation of histone H3 lysine 9 and H3 lysine 27 during X chromosome inactivation in three types of cells. Li, Yan; Tan, Tan; Zong, Le; He, Dacheng; Tao, Wei; Liang, Qianjin // Chromosome Research;Aug2012, Vol. 20 Issue 6, p769 

    Histone methylation is one epigenetic modification of an inactive X chromosome (Xi). Histone H3 lysine 9 dimethylation (H3K9me) and histone H3 lysine 27 trimethylation (H3K27me) are both associated with the chromatin of gene-silenced regions in the X chromosome and with X inactivation. Studies...

  • Different Polycomb group complexes regulate common target genes in Arabidopsis. Makarevich, Grigory; Leroy, Olivier; Akinci, Umut; Schubert, Daniel; Clarenz, Oliver; Goodrich, Justin; Grossniklaus, Ueli; Köhler, Claudia // EMBO Reports;Sep2006, Vol. 7 Issue 9, p947 

    Polycomb group (PcG) proteins convey epigenetic inheritance of repressed transcriptional states. Although the mechanism of the action of PcG is not completely understood, methylation of histone H3 lysine 27 (H3K27) is important in establishing PcG-mediated transcriptional repression. We show...

  • Small RNAs Prevent Transcription-Coupled Loss of Histone H3 Lysine 9 Methylation in Arabidopsis thaliana. Enke, Raymond A.; Dong, Zhicheng; Bender, Judith // PLoS Genetics;Oct2011, Vol. 7 Issue 10, Special section p1 

    In eukaryotes, histone H3 lysine 9 methylation (H3K9me) mediates silencing of invasive sequences to prevent deleterious consequences including the expression of aberrant gene products and mobilization of transposons. In Arabidopsis thaliana, H3K9me maintained by SUVH histone methyltransferases...

  • Inner workings and regulatory inputs that control Polycomb repressive complex 2. O'Meara, M.; Simon, Jeffrey // Chromosoma;Jun2012, Vol. 121 Issue 3, p221 

    Polycomb repressive complex 2 (PRC2) is a conserved multisubunit enzyme that methylates histone H3 on lysine-27. This chromatin modification is a hallmark of target genes transcriptionally silenced by the Polycomb system. At its core, PRC2 activity depends upon the SET domain active site of its...

  • SETDB1 Is Involved in Postembryonic DNA Methylation and Gene Silencing in Drosophila. Gou, Dawei; Rubalcava, Monica; Sauer, Silvia; Mora-Bermúdez, Felipe; Erdjument-Bromage, Hediye; Tempst, Paul; Kremmer, Elisabeth; Sauer, Frank // PLoS ONE;2010, Vol. 5 Issue 5, p1 

    DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics