Confining euchromatin/heterochromatin territory: <i>jumonji</i> crosses the line

Tamaru, Hisashi

doi:10.1101/gad.1941010

Cited by 91 publications

(66 citation statements)

References 163 publications

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“…initial nucleation event positions HP1 complexes containing H3K9 methyltransferases on the chromatin (20,37). Subsequent cycles of H3K9 methylation and loading of HP1 complexes result in the spreading of heterochromatin along the chromatin (26,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…However, because H3K9me3 is primarily located within silent, heterochromatic regions (20,37,38), this requirement suggests that Tip60 activity during DNA repair may be restricted to chromatin domains with a high density of H3K9me2/3. Here, we demonstrate that transient loading of kap-1/HP1/suv39h1 at DSBs provides a mechanism for rapidly increasing H3K9me3 in open (euchromatin) domains that lack preexisting H3K9me3.…”

Section: Discussionmentioning

confidence: 99%

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DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin

Ayrapetov

Gürsoy-Yüzügüllü

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

319

335

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Dynamic changes in histone modification are critical for regulating DNA double-strand break (DSB) repair. Activation of the Tip60 acetyltransferase by DSBs requires interaction of Tip60 with histone H3 methylated on lysine 9 (H3K9me3). However, how H3K9 methylation is regulated during DSB repair is not known. Here, we demonstrate that a complex containing kap-1, HP1, and the H3K9 methyltransferase suv39h1 is rapidly loaded onto the chromatin at DSBs. Suv39h1 methylates H3K9, facilitating loading of additional kap-1/HP1/suv39h1 through binding of HP1's chromodomain to the nascent H3K9me3. This process initiates cycles of kap-1/HP1/ suv39h1 loading and H3K9 methylation that facilitate spreading of H3K9me3 and kap-1/HP1/suv39h1 complexes for tens of kilobases away from the DSB. These domains of H3K9me3 function to activate the Tip60 acetyltransferase, allowing Tip60 to acetylate both ataxia telangiectasia-mutated (ATM) kinase and histone H4. Consequently, cells lacking suv39h1 display defective activation of Tip60 and ATM, decreased DSB repair, and increased radiosensitivity. Importantly, activated ATM rapidly phosphorylates kap-1, leading to release of the repressive kap-1/HP1/suv39h1 complex from the chromatin. ATM activation therefore functions as a negative feedback loop to remove repressive suv39h1 complexes at DSBs, which may limit DSB repair. Recruitment of kap-1/HP1/suv39h1 to DSBs therefore provides a mechanism for transiently increasing the levels of H3K9me3 in open chromatin domains that lack H3K9me3 and thereby promoting efficient activation of Tip60 and ATM in these regions. Further, transient formation of repressive chromatin may be critical for stabilizing the damaged chromatin and for remodeling the chromatin to create an efficient template for the DNA repair machinery.histone methylation | homologous recombination D NA double-strand breaks (DSBs) are toxic and must be repaired to maintain genomic stability. Detection of DSBs requires recruitment of the mre11-rad50-nbs1 (MRN) complex to the DNA ends (1). MRN then recruits and activates the ataxia telangiectasia-mutated (ATM) kinase (2, 3) through a mechanism that also requires the Tip60 acetyltransferase (3). Tip60 directly acetylates and activates ATM's kinase activity (4-6) and functions, in combination with MRN, to promote ATM-dependent phosphorylation of DSB repair proteins (3), including histone H2AX. This process creates domains of phosphorylated H2AX (γH2AX) extending for hundreds of kilobases along the chromatin (7,8). Mdc1 then binds to γH2AX, providing a landing pad for other DSB repair proteins, including the RNF8/RNF168 ubiquitin ligases (1, 3, 9, 10). Tip60 also plays a critical role in regulating chromatin structure at DSBs as part of the NuA4-Tip60 complex (11). NuA4-Tip60 catalyzes histone exchange (via the p400 ATPase subunit) and acetylation of histone H4 (by Tip60) at DSBs (12-15), leading to the formation of open, flexible chromatin domains adjacent to the break (12, 13). These open chromatin structures then facilitate histone ub...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin

Ayrapetov

Gürsoy-Yüzügüllü

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

319

335

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“…As discussed for the G9a/GLP complex, it is interesting to address the functional significance of a complex possessing multiple (four in this case) HKMTs with the same substrate (H3K9) specificity. Finally, in plants and the yeast Schizosaccharomyces pombe, the RNAi machinery is integrated with the regulation of H3K9 methylation (Grewal 2010;Tamaru 2010). While the RNAi machinery is also conserved in mammals, it is not clear whether this system is involved in G9a/GLP-mediated H3K9 methylation.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, the DIM-2-HP1 complex is recruited to H3K9me3-positive nucleosome loci via HP1 binding to H3K9me3 and induces DNA methylation. In Arabidopsis, DNA methylation and H3K9 methylation are functionally interdependent (Jackson et al 2002;Malagnac et al 2002;Johnson et al 2007;Tamaru 2010). The SET-or RING-associated (SRA) domain of the HKMT KRYPTONITE (KYP) binds to methylated DNA.…”

Section: Link Between H3k9 Methylation and Dna Methylationmentioning

confidence: 99%

H3K9 methyltransferase G9a and the related molecule GLP

Shinkai

Tachibana²

2011

Genes Dev.

504

442

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The discovery of Suv39h1, the first SET domain-containing histone lysine methyltransferase (HKMT), was reported in 2000. Since then, research on histone methylation has progressed rapidly. Among the identified HKMTs in mammals, G9a and GLP are the primary enzymes for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2), and exist predominantly as a G9a–GLP heteromeric complex that appears to be a functional H3K9 methyltransferase in vivo. Recently, many important studies have reported that G9a and GLP play critical roles in various biological processes. The physiological relevance of G9a/GLP-mediated epigenetic gene regulation is discussed.

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“…50 In particular, acetylation on histone H4 and methylation of lysine 9 on histone H3 can significantly influence chromatin structure of euchromatin (decondensed chromatin) and heterochromatin (highly condensed chromatin), respectively. [51][52][53][54] Hence, patterns of these histone modifications, collectively referred to as the "histone code" can physically regulate gene expression and transcription. 55 Currently, researchers commonly consider 24 histone modifications of acetylation and methylation on 22 modification sites (Fig.…”

Section: B Broad Variety Of Histone Modificationsmentioning

confidence: 99%

Micro- and nanofluidic technologies for epigenetic profiling

et al. 2013

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This short review provides an overview of the impact micro- and nanotechnologies can make in studying epigenetic structures. The importance of mapping histone modifications on chromatin prompts us to highlight the complexities and challenges associated with histone mapping, as compared to DNA sequencing. First, the histone code comprised over 30 variations, compared to 4 nucleotides for DNA. Second, whereas DNA can be amplified using polymerase chain reaction, chromatin cannot be amplified, creating challenges in obtaining sufficient material for analysis. Third, while every person has only a single genome, there exist multiple epigenomes in cells of different types and origins. Finally, we summarize existing technologies for performing these types of analyses. Although there are still relatively few examples of micro- and nanofluidic technologies for chromatin analysis, the unique advantages of using such technologies to address inherent challenges in epigenetic studies, such as limited sample material, complex readouts, and the need for high-content screens, make this an area of significant growth and opportunity.

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Confining euchromatin/heterochromatin territory: jumonji crosses the line

Cited by 91 publications

References 163 publications

DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin

DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin

H3K9 methyltransferase G9a and the related molecule GLP

Micro- and nanofluidic technologies for epigenetic profiling

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