COMPASS, a Histone H3 (Lysine 4) Methyltransferase Required for Telomeric Silencing of Gene Expression

Krogan, Nevan J.; Dover, Jim; Khorrami, Shahram; Greenblatt, Jack; Schneider, Jessica; Johnston, Mark; Shilatifard, Ali

doi:10.1074/jbc.c200023200

Cited by 375 publications

(372 citation statements)

References 29 publications

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“…For a wild-type strain, H3K4 mono-, di-, and trimethylation was readily detected in total cell extracts but no methylation was detected in the DAn-set1 or DAn-swd1 strains ( Figure S2). This result is consistent with the Set1 complex mediating mono-, di-, and trimethylation at histone H3K4 in A. nidulans, similar to other organisms (Krogan et al 2002;Noma and Grewal 2002;Dehe and Geli 2006;Shilatifard 2012;Palmer et al 2013).In addition to the methylation of H3 at K4, the Set1 complex has also been shown to methylate the kinetochore protein Dam1 in S. cerevisiae (Zhang et al 2005). To determine whether the histone H3K4 target site of the Set1 complex was involved in the synthetic growth defects with partial NIMA or CDK1 function (Figure 1), we generated strains carrying a mutant version of histone H3, where the lysine K4 was changed to arginine (H3K4R).…”

supporting

confidence: 78%

“…Taken together, our data show that An-swd1 is essential when the function of either NIMA or CDK1 mitotic kinase is partially inhibited. Swd1 is essential for the function of the Set1 complex (Krogan et al 2002;Nagy et al 2002), and therefore it is likely that the genetic interaction between An-swd1 and the mitotic kinases is due to the absence of Set1 complexmediated methylation. However it is possible that An-swd1 plays other functions independent of the Set1 complex.…”

Section: Resultsmentioning

confidence: 99%

“…Set1 complex-mediated methylation of H3K4 is found most commonly on actively transcribed genes (Dehe and Geli 2006). In addition, H3K4 methylation is also involved in maintaining the repression of telomere proximal genes in S. cerevisiae and Schizosaccharomyces pombe and the suppression of secondary metabolite production in A. nidulans and A. fumigatus (Krogan et al 2002;Kanoh et al 2003;Bok et al 2009;Palmer et al 2013). Growing evidence indicates that the Set1 complex is involved in a gamut of additional cellular functions, many of which may be independent of its roles in gene expression, including kinetochore maintenance, DNA repair, and replication checkpoints (Faucher and Wellinger 2010;Bergmann et al 2011).…”

mentioning

confidence: 99%

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The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast.D URING the transition from interphase into mitosis, chromatin undergoes dramatic global restructuring to go from a relaxed interphase configuration amenable to gene expression to a condensed form characteristic of mitotic chromosomes. Chromatin condensation not only marks mitosis but is also essential for the normal segregation of the duplicated sister chromatids into daughter nuclei. On the other hand, during mitotic exit, decondensation of chromatin needs to be triggered in a correct temporal manner to enable successful transition into interphase. In Aspergillus nidulans, a model filamentous fungus that enabled discovery of cell cycle-specific genes, mitotic initiation requires the function of the essential NIMA mitotic kinase (Oakley and Morris 1983;Osmani et al. 1987). Early evidence pointed to a role for NIMA in regulating chromatin compaction through the cell cycle since overexpression of NIMA was sufficient to induce chromatin condensation independent of cell cycle phase (Osmani et al. 1988;. Importantly, NIMA is required for, and can promote, the phosphorylation of histone H3 at serine 10 (De Souza et al. 2000), a universal marker of mitotic chromatin. In addition, NIMA has been shown to regulate the partial disassembly of nuclear pore complexes, allowing the access of mitotic regulators to the nucleus (Wu et al. 1998;De S...

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supporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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“…In S. cerevisiae the COMPASS histone methyltransferase carries out telomeric silencing of gene expression 33 . The P. stipitis genome contains a COMPASS homolog (SET1), so the same mechanism might be functioning here.…”

Section: Discussionmentioning

confidence: 99%

Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis

Jeffries

Grigoriev

Grimwood³

et al. 2007

Nat Biotechnol

443

313

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Xylose is a major constituent of plant lignocellulose, and its fermentation is important for the bioconversion of plant biomass to fuels and chemicals. Pichia stipitis is a well-studied, native xylose-fermenting yeast. The mechanism and regulation of xylose metabolism in P. stipitis have been characterized and genes from P. stipitis have been used to engineer xylose metabolism in Saccharomyces cerevisiae. We have sequenced and assembled the complete genome of P. stipitis. The sequence data have revealed unusual aspects of genome organization, numerous genes for bioconversion, a preliminary insight into regulation of central metabolic pathways and several examples of colocalized genes with related functions. The genome sequence provides insight into how P. stipitis regulates its redox balance while very efficiently fermenting xylose under microaerobic conditions.

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“…The first H3K4 methylase complex, COMPASS, was identified in the yeast S. cerevisiae and consists of Set1/KMT2 and seven other polypeptides (named Cps60-Cps15) [24]. Set1/KMT2 alone is not enzymatically active, but functions within COMPASS and is capable of mono-, di-, and trimethylating H3K4 [6,8,10,[24][25][26][27]. Following the identification of Set1/COMPASS as an H3K4 methylase, it was demonstrated that its mammalian homologues, the MLL proteins, MLL1-4 and hSet1A and B, are found in COMPASS-like complexes capable of methylating the fourth lysine of histone H3 [6,28,29] (Figure 2).…”

Section: Enzymatic Machinery Required For H3k4 Methylationmentioning

confidence: 99%

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

Shilatifard

2008

Current Opinion in Cell Biology

Self Cite

427

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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COMPASS, a Histone H3 (Lysine 4) Methyltransferase Required for Telomeric Silencing of Gene Expression

Cited by 375 publications

References 29 publications

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis

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

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