Transitions in Distinct Histone H3 Methylation Patterns at the Heterochromatin Domain Boundaries

Noma, Ken-ichi; Allis, C. David; Grewal, Shiv I. S.

doi:10.1126/science.1064150

Cited by 684 publications

(589 citation statements)

References 25 publications

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“…This finding was somewhat unexpected but consistent with the study by Shnyreva et al (12). Furthermore, in many other recent studies that identified active histone modifications, for example, in the cluster of the globin genes (41), the mating type locus in yeast (42), the Hoxd4 locus (43), active histone modifications do not always correlate with gene expression. Therefore, we believe that for the IFN-␥ gene, the lack of H3K4me2 modification is not an essential condition for silencing its expression in the day 5 Th2 cells.…”

Section: Discussionsupporting

confidence: 86%

Temporal and Spatial Changes of Histone 3 K4 Dimethylation at the IFN-γ Gene during Th1 and Th2 Cell Differentiation

Hamalainen-Laanaya¹,

Kobie²,

Chang

et al. 2007

The Journal of Immunology

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Covalent modification of nucleosomal histones is an important mechanism for cytokine gene regulation in Th1 and Th2 cells. In this study, we analyzed the kinetics of histone H3 K4 dimethylation (H3K4me2) of the IFN-γ gene. Minimal levels of H3K4me2 were found in naive CD4 T cells. After 5 days of differentiation, H3K4me2 levels were elevated in both Th1 and Th2 cells at the −5.3 kb, the promoter, the intronic DNase I hypersensitive sites, and 3′ distal sites including the +9.5 kb and +16 kb sites. Th1 cells maintained high levels of H3K4me2 after longer time of culture. However, in Th2 cells after 14 days, high levels of H3K4me2 were detected only at the −5.3 kb and the promoter, whereas H3K4me2 was lost at the 3′ distal sites and greatly diminished at the DNase I hypersensitive sites. After 28 days, Th2 cells lose H3K4me2 at all sites. Unlike the long-term primary Th2 cells, the Th2 clone D10 showed strong H3K4me2 at the IFN-γ gene with distinctly high levels at the 3′ distal sites. CD4 T cells transgenic for Hlx or infected with T-bet-expressing retrovirus produced IFN-γ and retained high levels of H3K4me2 even after differentiated under Th2 polarizing conditions, suggesting positive roles of these two factors in maintaining high levels of H3K4me2 at the IFN-γ gene.

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Section: Discussionsupporting

confidence: 86%

Temporal and Spatial Changes of Histone 3 K4 Dimethylation at the IFN-γ Gene during Th1 and Th2 Cell Differentiation

Hamalainen-Laanaya¹,

Kobie²,

Chang

et al. 2007

The Journal of Immunology

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“…Hyperacetylation of histone H3 and H4 lysine residues is generally associated with active chromatin, whereas deacetylation has been correlated with inactive genes (35). Another histone modification that has been associated with transcriptionally active chromatin is methylation at Lys 4 of histone H3 (36,37). In cancer cells, histone modifications work in concert with DNA methylation to silence tumor suppressor genes (13,28,38).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Tumor Endothelial Cell Anergy: Silencing of Intercellular Adhesion Molecule-1 by Histone Modifications

Hellebrekers

Castermans

Viré³

et al. 2006

Cancer Research

142

107

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Tumors can escape from immunity by repressing leukocyte adhesion molecule expression on tumor endothelial cells and by rendering endothelial cells unresponsive to inflammatory activation. This endothelial cell anergy is induced by angiogenic growth factors and results in reduced leukocytevessel wall interactions, thereby attenuating infiltration of leukocytes into the tumor. This report describes a novel mechanism of endothelial cell anergy regulation. We recently reported that DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors have angiostatic activity. Here, we studied whether epigenetic mechanisms regulate this angiogenesis-mediated escape from immunity. We found that DNMT inhibitors 5-aza-2 ¶-deoxycytidine and zebularine, as well as HDAC inhibitor trichostatin A, reexpressed intercellular adhesion molecule-1 (ICAM-1) on tumor-conditioned endothelial cells in vitro , resulting in restored leukocyte-endothelial cell adhesion. In addition, treatment with DNMT or HDAC inhibitors in vivo also restored ICAM-1 expression on tumor endothelial cells from two different mouse tumor models. Furthermore, leukocyte-vessel wall interactions in mouse tumors were increased by these compounds, as measured by intravital microscopy, resulting in enhanced leukocyte infiltration. We show that ICAM-1 down-regulation in tumor endothelial cells is associated with ICAM-1 promoter histone H3 deacetylation and loss of histone H3 Lys 4 methylation but not with DNA hypermethylation. In conclusion, our data show that ICAM-1 is epigenetically silenced in tumor endothelial cells by promoter histone modifications, which can be overcome by DNMT and HDAC inhibitors, suggesting a new molecular mechanism based on which novel therapeutic approaches for cancer can be

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“…Histone methylation could either be associated with actively transcribing RNA polymerase II (Pol II) or could be involved in setting the stage for transcriptional repression within heterochromatin, and sometimes could be both [6,9,[11][12][13]. For example, histone H3 lysine 9 methylation (H3K9), which is implemented by the SUV39 family of enzymes, is mostly associated with the silent regions within both euchromatin and heterochromatin [14][15][16][17][18]. The SUV39 family of HMTs contains a cysteine rich pre-SET domain, which is required for specificity towards H3K9 [18].…”

Section: Nih Public Accessmentioning

confidence: 99%

Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

Shilatifard

2008

Current Opinion in Cell Biology

434

408

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Chromosomal surfaces are ornamented with a variety of posttranslational modifications of histones, which are required for the regulation of many of the DNA-templated processes. Such histone modifications include acetylation, sumoylation, phosphorylation, ubiquitination and methylation. Histone modifications can either function by disrupting chromosomal contacts or by regulating nonhistone protein interactions with chromatin. In this review, recent findings will be discussed regarding the regulation of the implementation and physiological significance for one such histone modification, histone H3 Lysine 4 (H3K4) methylation by the yeast COMPASS and mammalian COMPASS-like complexes.All DNA-templated processes are regulated by chromatin and its posttranslational modifications. The nucleosome, which is the fundamental unit of chromatin, is composed of 146 base pairs of DNA wrapped twice around an octamer of the four core histones (H3, H4, H2A, and H2B) [1][2][3]. Structural studies demonstrated that the unstructured histone N-terminal tails protrude outward from the nucleosomes and are available for interactions with other neighboring histones or non-histone proteins. Many residues within the histone N-terminal tails and a few within the histone core can be altered by posttranslational modifications [1]. To date, there are at least five types of posttranslational modifications found on histones, these include: acetylation, phosphorylation, ubiquitination, sumoylation, and methylation [4,5]. Almost all of these modifications have been shown to be reversible, and their implementation and removal are fundamental to the regulation of a diverse set of biological processes such as replication, repair, recombination, transcription and RNA processing [4,5]. This review will focus mainly on the most recent studies of one type of histone modification, histone H3 lysine 4 (H3K4) methylation. Histone lysine methylationHistones are methylated either on their arginine and/or lysine residues [6,7]. The lysine residues are methylated on the ε-nitrogen by either the SET domain or the non-SET domain-containing lysine methyltransferases (KMTs). A large number of enzymes have been characterized which are capable of methylating specific lysine residues on histones ( Table 1). The ε-nitrogen can also be modified by lysine acetyl transferases (KATs) and methylation and acetylation of lysine are mutually exclusive. Indeed, many sites of histone methylation are also sites of acetylation.Correspondence and proofs should be sent to the following address: Ali Shilatifard, Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, Office (816) 926-4465, Email: ASH@Stowers-Institute.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable for...

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Transitions in Distinct Histone H3 Methylation Patterns at the Heterochromatin Domain Boundaries

Cited by 684 publications

References 25 publications

Temporal and Spatial Changes of Histone 3 K4 Dimethylation at the IFN-γ Gene during Th1 and Th2 Cell Differentiation

Temporal and Spatial Changes of Histone 3 K4 Dimethylation at the IFN-γ Gene during Th1 and Th2 Cell Differentiation

Epigenetic Regulation of Tumor Endothelial Cell Anergy: Silencing of Intercellular Adhesion Molecule-1 by Histone Modifications

Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

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