scholarly journals MET-2, a SETDB1 family methyltransferase, coordinates embryo events through distinct histone H3 methylation states

2018 ◽  
Author(s):  
Beste Mutlu ◽  
Huei-Mei Chen ◽  
David H. Hall ◽  
Susan E. Mango
Keyword(s):  
Developmental Plasticity ◽  
Histone H3 ◽  
Cell Counting ◽  
H3k9 Methylation ◽  
Developmental Potential ◽  
Heterochromatin Formation ◽  
Histone H3 Methylation ◽  
Summary Statement ◽  
Genome Activation ◽  
The Relationship

AbstractDuring the first hours of embryogenesis, formation of higher-order heterochromatin coincides with the loss of developmental potential. Here we examine the relationship between these two processes, and we probe the determinants that contribute to their onset. Mutations that disrupt histone H3 lysine 9 (H3K9) methyltransferases reveal that the methyltransferase MET-2 helps terminate developmental plasticity, likely through mono- and di- methylation of H3K9 (me1/me2), and promotes heterochromatin formation, likely through H3K9me3. We examine how MET-2 is regulated and find that methylated H3K9 appears gradually and depends on the accumulated time of embryogenesis. H3K9me is independent of zygotic genome activation or cell counting. These data reveal how central events are synchronized during embryogenesis and distinguish distinct roles for different H3K9 methylation states.Summary StatementDuring early embryogenesis, heterochromatin formation and loss of developmental plasticity are coordinately regulated by distinct Histone H3 Lysine 9 (H3K9) methylation states, by the methyltransferase MET-2.

scholarly journals SUV39 SET domains mediate crosstalk of heterochromatic histone marks

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alessandro Stirpe ◽  
Nora Guidotti ◽  
Sarah J Northall ◽  
Sinan Kilic ◽  
Alexandre Hainard ◽  
...  
Keyword(s):  
Structure Function ◽  
Fission Yeast ◽  
Catalytic Domain ◽  
Constitutive Heterochromatin ◽  
Histone H3 ◽  
H3k9 Methylation ◽  
Set Domain ◽  
Heterochromatin Formation ◽  
Heterochromatin Silencing ◽  
Genomic Regions

The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.

scholarly journals Telomere repeats induce domains of H3K27 methylation in Neurospora

2017 ◽  
Author(s):  
Kirsty Jamieson ◽  
Kevin J. McNaught ◽  
Tereza Ormsby ◽  
Neena A. Leggett ◽  
Shinji Honda ◽  
...  
Keyword(s):  
Genome Organization ◽  
Chromosomal Rearrangements ◽  
Histone H3 ◽  
Facultative Heterochromatin ◽  
Large Domain ◽  
Heterochromatin Formation ◽  
H3k27 Methylation ◽  
And Control ◽  
The Relationship ◽  
Insight Into

ABSTRACTDevelopment in higher organisms requires selective gene silencing, directed in part by di-/tri-methylation of lysine 27 on histone H3 (H3K27me2/3). Knowledge of the cues that control formation of such repressive Polycomb domains is extremely limited. We exploited natural and engineered chromosomal rearrangements in the fungus Neurospora crassa to elucidate the control of H3K27me2/3. Analyses of H3K27me2/3 in strains bearing chromosomal rearrangements revealed both position-dependent and position-independent facultative heterochromatin. We found that proximity to chromosome ends is necessary to maintain, and sufficient to induce, transcriptionally repressive, subtelomeric H3K27me2/3. We ascertained that such telomere-proximal facultative heterochromatin requires native telomere repeats and found that a short array of ectopic telomere repeats, (TTAGGG)17, can induce a large domain (∼225 kb) of H3K27me2/3. This provides an example of a cis-acting sequence that directs H3K27 methylation. Our findings provide new insight into the relationship between genome organization and control of heterochromatin formation.

The Relationship Between DOT1L, Histone H3 Methylation, and Genome Stability in Cancer

2017 ◽  
Vol 3 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Brent J. Guppy ◽  
Lucile M-P. Jeusset ◽  
Kirk J. McManus
Keyword(s):  
Genome Stability ◽  
Histone H3 ◽  
Histone H3 Methylation ◽  
The Relationship

scholarly journals Telomere repeats induce domains of H3K27 methylation in Neurospora

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kirsty Jamieson ◽  
Kevin J McNaught ◽  
Tereza Ormsby ◽  
Neena A Leggett ◽  
Shinji Honda ◽  
...  
Keyword(s):  
Genome Organization ◽  
Chromosomal Rearrangements ◽  
Histone H3 ◽  
Facultative Heterochromatin ◽  
Heterochromatin Formation ◽  
Cis Acting ◽  
H3k27 Methylation ◽  
And Control ◽  
The Relationship ◽  
Insight Into

Development in higher organisms requires selective gene silencing, directed in part by di-/trimethylation of lysine 27 on histone H3 (H3K27me2/3). Knowledge of the cues that control formation of such repressive Polycomb domains is extremely limited. We exploited natural and engineered chromosomal rearrangements in the fungus Neurospora crassa to elucidate the control of H3K27me2/3. Analyses of H3K27me2/3 in strains bearing chromosomal rearrangements revealed both position-dependent and position-independent facultative heterochromatin. We found that proximity to chromosome ends is necessary to maintain, and sufficient to induce, transcriptionally repressive, subtelomeric H3K27me2/3. We ascertained that such telomere-proximal facultative heterochromatin requires native telomere repeats and found that a short array of ectopic telomere repeats, (TTAGGG)17, can induce a large domain (~225 kb) of H3K27me2/3. This provides an example of a cis-acting sequence that directs H3K27 methylation. Our findings provide new insight into the relationship between genome organization and control of heterochromatin formation.

Caught in conspiracy: cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin

2005 ◽  
Vol 83 (3) ◽  
pp. 385-395 ◽  
Author(s):  
Irina Stancheva
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Interference ◽  
Histone Methylation ◽  
Functional Relationship ◽  
Histone H3 ◽  
H3k9 Methylation ◽  
Complex Interactions ◽  
Histone H3 Methylation ◽  
Intensive Investigation

Heritable patterns of gene expression and gene silencing are determined by chromatin states that either permit or restrict transcription. Restrictive heterochromatin in most eukaryotes is characterized by high levels of DNA methylation and histone H3 methylation at lysine 9. The functional relationship between these two modifications is the focus of intensive investigation in various organisms from fungi to mammals. Complex interactions have been discovered among various components of DNA methylation and histone methylation pathways, proteins involved in the formation of higher-order chromatin structure, chromatin remodelling activities, and RNA interference. This review discusses some aspects of this crosstalk and the cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin.Key words: DNA methylation, H3K9 methylation, heterochromatin.

scholarly journals Restricted epigenetic inheritance of H3K9 methylation

Science ◽  
2015 ◽  
Vol 348 (6230) ◽  
pp. 132-135 ◽  
Author(s):  
Pauline N. C. B. Audergon ◽  
Sandra Catania ◽  
Alexander Kagansky ◽  
Pin Tong ◽  
Manu Shukla ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Histone Demethylase ◽  
Epigenetic Mark ◽  
H3k9 Methylation ◽  
Silent Chromatin ◽  
Wild Type ◽  
Heterochromatin Formation ◽  
Posttranslational Histone Modifications

Posttranslational histone modifications are believed to allow the epigenetic transmission of distinct chromatin states, independently of associated DNA sequences. Histone H3 lysine 9 (H3K9) methylation is essential for heterochromatin formation; however, a demonstration of its epigenetic heritability is lacking. Fission yeast has a single H3K9 methyltransferase, Clr4, that directs all H3K9 methylation and heterochromatin. Using releasable tethered Clr4 reveals that an active process rapidly erases H3K9 methylation from tethering sites in wild-type cells. However, inactivation of the putative histone demethylase Epe1 allows H3K9 methylation and silent chromatin maintenance at the tethering site through many mitotic divisions, and transgenerationally through meiosis, after release of tethered Clr4. Thus, H3K9 methylation is a heritable epigenetic mark whose transmission is usually countered by its active removal, which prevents the unauthorized inheritance of heterochromatin.

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