Functional Characterization of the Drosophila Hmt4-20/Suv4-20 Histone Methyltransferase

Sakaguchi, Ayako; Karachentsev, Dmitry; Seth-Pasricha, Mansha; Druzhinina, Marina; Steward, Ruth

doi:10.1534/genetics.108.087650

Cited by 42 publications

(39 citation statements)

References 26 publications

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“…6), suggesting that SET-4 may antagonize H4K20 monomethylation on autosomes. This finding is consistent with the observed increase in H4K20me1 levels in flies carrying a mutation in the set-4 homolog Suv4-20 (64). Western blot analysis also revealed that SET-4 activity is needed for wild-type levels of H4K20me3 (Fig.…”

Section: Figsupporting

confidence: 90%

Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

et al. 2012

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Dosage compensation equalizes X-linked gene expression between the sexes. This process is achieved in Caenorhabditis elegans by hermaphrodite-specific, dosage compensation complex (DCC)-mediated, 2-fold X chromosome downregulation. How the DCC downregulates gene expression is not known. By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. Depletion of H4K16ac also requires the conserved histone deacetylase SIR-2.1, while enrichment of H4K20me1 requires the activities of the histone methyltransferases SET-1 and SET-4. Our data suggest that the mechanism of dosage compensation in C. elegans involves redistribution of chromatin-modifying activities, leading to a depletion of H4K16ac and an enrichment of H4K20me1 on the X chromosomes. These results support conserved roles for histone H4 chromatin modification in worm dosage compensation analogous to those seen in flies, using similar elements and opposing strategies to achieve differential 2-fold changes in X-linked gene expression.

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Section: Figsupporting

confidence: 90%

Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

et al. 2012

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“…Thus, a change in methyltransferase protein levels or modulation of methyltransferase activity by other histone modifications or by modifications on the enzymes themselves could account for the latency of H3K9 and H3K27 trimethylation. The absence of appreciable turnover at these residues is similar to the lack of H4K20me3 turnover across the cell cycle (39), where H4K20me3 was initially implicated in position effect variegation silencing, such as that for H3K9me3, but has recently been questioned as an epigenetic silencing mark (44). Furthermore, ectopic overexpression of EZH2, and presumably increased H3K27 trimethylation, accelerates G 1 -phase progression and leads to increased accumulation in S phase (8).…”

Section: Discussionmentioning

confidence: 77%

Origins and Formation of Histone Methylation across the Human Cell Cycle

Zee

Britton

Wolle

et al. 2012

Molecular and Cellular Biology

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The connections between various nuclear processes and specific histone posttranslational modifications are dependent to a large extent on the acquisition of those modifications after histone synthesis. The reestablishment of histone posttranslational modifications after S phase is especially critical for H3K9 and H3K27 trimethylation, both of which are linked with epigenetic memory and must be stably transmitted from one cellular generation to the next. This report uses a proteomic strategy to interrogate how and when the cell coordinates the formation of histone posttranslational modifications during division. Paramount among the findings is that H3K9 and H3K27 trimethylation begins during S phase but is completed only during the subsequent G 1 phase via two distinct pathways from the unmodified and preexisting dimethylated states. In short, we have systematically characterized the temporal origins and methylation pathways for histone posttranslational modifications during the cell cycle.

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“…Similarly, several lines of evidence have pointed to an interaction between HP1 and the H4K20 HMT Suv4-20 in mammalian systems, including in vitro pull down assays using mammalian proteins and a requirement for Suvar3-9h for proper distribution of H4K20me ). Suv4-20 has been reported to act as a suppressor of PEV in Drosophila; however, this activity appears to be dependent upon the allele and reporter combination being examined Sakaguchi et al 2008). Our results demonstrate an in vivo interaction between HP1 and Suv4-20 in Drosophila and support a yet-to-be-defined role for H4K20 in heterochromatic regions.…”

Section: Drosophila Heterochromatin Spreading 973mentioning

confidence: 99%

Domains of Heterochromatin Protein 1 Required forDrosophila melanogasterHeterochromatin Spreading

et al. 2009

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Centric regions of eukaryotic genomes are packaged into heterochromatin, which possesses the ability to spread along the chromosome and silence gene expression. The process of spreading has been challenging to study at the molecular level due to repetitious sequences within centric regions. A heterochromatin protein 1 (HP1) tethering system was developed that generates ''ectopic heterochromatin'' at sites within euchromatic regions of the Drosophila melanogaster genome. Using this system, we show that HP1 dimerization and the PxVxL interaction platform formed by dimerization of the HP1 chromo shadow domain are necessary for spreading to a downstream reporter gene located 3.7 kb away. Surprisingly, either the HP1 chromo domain or the chromo shadow domain alone is sufficient for spreading and silencing at a downstream reporter gene located 1.9 kb away. Spreading is dependent on at least two H3K9 methyltransferases, with SU(VAR)3-9 playing a greater role at the 3.7-kb reporter and dSETDB1 predominately acting at the 1.9 kb reporter. These data support a model whereby HP1 takes part in multiple mechanisms of silencing and spreading.H ETEROCHROMATIN protein 1 (HP1) was identified in Drosophila as a nonhistone chromosomal protein enriched in centric heterochromatin ( James and Elgin 1986;James et al. 1989). On polytene chromosomes, HP1 localizes near centromeres and telomeres, along the fourth chromosome and at $200 sites within the euchromatic arms ( James et al. 1989;Fanti et al. 2003). Heterochromatin has the ability to ''spread,'' or propagate in cis, along the chromosome (Weiler and Wakimoto 1995). Spreading is observed when a chromosomal rearrangement places a euchromatic domain next to a heterochromatic domain. Cytologically, spreading is visualized as densely compact chromatin that emanates from the chromocenter, the structure formed by the fusion of centromeres, and extends into the banded regions of polytene chromosomes (Belyaeva and Zhimulev 1991). Euchromatic genes brought into juxtaposition with heterochromatin by chromosomal rearrangements exhibit gene silencing, termed position effect variegation (PEV) (Weiler and Wakimoto 1995). Mutations in Su(var)2-5, the gene encoding HP1, suppress silencing, suggesting HP1 plays a key role in spreading (Eissenberg et al. 1990). The molecular processes of spreading are not well understood.Repetitive sequences within heterochromatin make it difficult to study spreading at the molecular level. In addition, specific repetitive elements are thought to function as initiation sites for heterochromatin formation (Sun et al. 2004;Haynes et al. 2006), making it challenging to separate initiation from spreading. To overcome these problems, we generated a system that nucleates small domains (,20 kb) of repressive chromatin that share many properties with centric heterochromatin. Here we refer to these as ectopic heterochromatin domains. These domains are generated by expressing a fusion protein, consisting of the DNA binding domain of the Escherichia coli lac represso...

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Functional Characterization of the Drosophila Hmt4-20/Suv4-20 Histone Methyltransferase

Cited by 42 publications

References 26 publications

Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

Origins and Formation of Histone Methylation across the Human Cell Cycle

Domains of Heterochromatin Protein 1 Required forDrosophila melanogasterHeterochromatin Spreading

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