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As a key epigenetic modification, the methylation of histone H3 lysine 36 (H3K36) modulates chromatin structure and is involved in diverse biological processes. To better understand the language of H3K36 methylation in rice (Oryza sativa), we chose potential histone methylation enzymes for functional exploration. In particular, we characterized rice SET DOMAIN GROUP 708 (SDG708) as an H3K36-specific methyltransferase possessing the ability to deposit up to three methyl groups on H3K36. Compared with the wild-type, SDG708-knockdown rice mutants displayed a late-flowering phenotype under both long-day and short-day conditions because of the down-regulation of the key flowering regulatory genes Heading date 3a (Hd3a), RICE FLOWERING LOCUS T1 (RFT1), and Early heading date 1 (Ehd1). Chromatin immunoprecipitation experiments indicated that H3K36me1, H3K36me2, and H3K36me3 levels were reduced at these loci in SDG708-deficient plants. More importantly, SDG708 was able to directly target and effect H3K36 methylation on specific flowering genes. In fact, knockdown of SDG708 led to misexpression of a set of functional genes and a genome-wide decrease in H3K36me1/2/3 levels during the early growth stages of rice. SDG708 is a methyltransferase that catalyses genome-wide deposition of all three methyl groups on H3K36 and is involved in many biological processes in addition to flowering promotion.Keywords:
Chromatin immunoprecipitation
Histone Methylation
Flowering Locus C
Although post-translational modifications (-PTMs) of some histone H3 lysine residues are well studied, the PTMs of histone H3 lysine 37 in mammalian cells remain largely unknown. In this study, we provide evidence to show that SMYD family member 5 (SMYD5) is a histone H3-specfic methyltransferase that catalyzes mono-methylation of H3 lysine 36 and 37 (H3K36/K37me1) in vitro. The site-mutagenesis analysis shows that a species-conserved histidine in its catalytic SET domain is required for its histone methyltransferase activity. Genetic deletion of Smyd5 in murine embryonic stem cells (mESCs) partially reduces the global histone H3K37me1 level in cells, suggesting SMYD5 is one of histone methyltransferases catalyzing histone H3K37me1 in vivo. Hence, our study reveals that SMYD5 is a histone H3-specific methyltransferase that mediates histone H3K36/K37me1, which provides a biochemical basis for further studying its functions in mammalian cells.
Histone Methylation
Histone octamer
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Histone Methylation
Chromatin immunoprecipitation
Histone code
Epigenomics
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Histone Methylation
Heterochromatin protein 1
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Covalent modification of histone tails is crucial for transcriptional regulation, mitotic chromosomal condensation, and heterochromatin formation. Histone H3 lysine 9 (H3-K9) methylation catalyzed by the Suv39h family proteins is essential for establishing the architecture of pericentric heterochromatin. We recently identified a mammalian histone methyltransferase (HMTase), G9a, which has strong HMTase activity towards H3-K9 in vitro. To investigate the in vivo functions of G9a, we generated G9a -deficient mice and embryonic stem (ES) cells. We found that H3-K9 methylation was drastically decreased in G9a -deficient embryos, which displayed severe growth retardation and early lethality. G9a -deficient ES cells also exhibited reduced H3-K9 methylation compared to wild-type cells, indicating that G9a is a dominant H3-K9 HMTase in vivo. Importantly, the loss of G9a abolished methylated H3-K9 mostly in euchromatic regions. Finally, G9a exerted a transcriptionally suppressive function that depended on its HMTase activity. Our results indicate that euchromatic H3-K9 methylation regulated by G9a is essential for early embryogenesis and is involved in the transcriptional repression of developmental genes.
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A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9 and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9 by the histone methyltransferase G9a was not affected by Set9 methylation of H3-K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in transcription activation by competing with histone deacetylases and by precluding H3-K9 methylation by Suv39h1. Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.
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Heterochromatin protein 1
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Histone Methylation
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Epigenomics
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Heterochromatin protein 1
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Gene expression within the context of eukaryotic chromatin is regulated by enzymes that catalyze histone lysine methylation. Histone lysine methyltransferases that have been identified to date possess the evolutionarily conserved SET or Dot1-like domains. We previously reported the identification of a new multi-subunit histone H3 lysine 4 methyltransferase lacking homology to the SET or Dot1 family of histone lysine methyltransferases. This enzymatic activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell. Here, we report that the minimal complex required for WRAD enzymatic activity includes WDR5, RbBP5, and Ash2L and that DPY-30, although not required for enzymatic activity, increases the histone substrate specificity of the WRAD complex. We also show that WRAD requires zinc for catalytic activity, displays Michaelis-Menten kinetics, and is inhibited by S-adenosyl-homocysteine. In addition, we demonstrate that WRAD preferentially methylates lysine 4 of histone H3 within the context of the H3/H4 tetramer but does not methylate nucleosomal histone H3 on its own. In contrast, we find that MLL1 and WRAD are required for nucleosomal histone H3 methylation, and we provide evidence suggesting that each plays distinct structural and catalytic roles in the recognition and methylation of a nucleosome substrate. Our results indicate that WRAD is a new H3K4 methyltransferase with functions that include regulating the substrate and product specificities of the MLL1 core complex.
Histone Methylation
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Histone Methylation
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histone H3 离氨酸 4 methyltransferases 的 MLL/SET 家庭与核心子单元 ASH2L， WDR5， RbBP5，和 DPY-30 (经常缩短的 WRAD ) 形成酶建筑群，并且为全球 histone H3 离氨酸 4 methylation 负责，在哺乳动物的房间的活跃地抄录的染色质的一个特点。因此，这些蛋白质的功能包括干细胞区别，房间生长和分割为许多过程被要求，身体分割，和造血作用。当 MLL-WRAD 上的大多数工作在 histone methylation 在功能上集中了这核心建筑群时，最近的研究显示 MLL-WRAD 蛋白质交往与许多另外的蛋白质和 lncRNAs 和罐头在原子核以外本地化到细胞的细胞器。在这评论，我们在内并且在原子核外面集中于最近描述的活动和 MLL-WRAD 的交往的搭挡。
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