The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes.

Tschiersch, B.; Hofmann, Annemarie; Krauß, Veiko; Dorn, Rainer; Korge, Günter; Reuter, Günter

doi:10.1002/j.1460-2075.1994.tb06693.x

Cited by 520 publications

(408 citation statements)

References 57 publications

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“…The C-terminal region of ALL-1 and TRX includes the SET domain, which is highly conserved between the two proteins and is also present within the trx-G/Pc-G proteins ASH1 (Tripoulas et al, 1996) and E(Z) (Jones and Gelbart, 1993), in the functionally related Drosophila protein SU(VAR) 3 ± 9 (Tschiersch et al, 1994), in the ALL-1 related protein ALR (Prasad et al, 1997), and in a series of other proteins from yeast, fungi, C. elegans, plants and humans (Jenuwein et al, 1998;Nislow et al, 1997;Prasad et al, 1997). A TRX C-terminal segment containing amino acid residues 3375 ± 3759, which span the SET motif and some upstream sequences, was inserted into the pGBT9 vector and used in a two hybrid assay to screen a Drosophila third instar larvae cDNA library in pACT.…”

Section: Resultsmentioning

confidence: 99%

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

et al. 2000

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The human ALL-1 gene is involved in acute leukemia through gene fusions, partial tandem duplications or a speci®c deletion. Several sequence motifs within the ALL-1 protein, such as the SET domain, PHD ®ngers and the region with homology to DNA methyl transferase are shared with other proteins involved in transcription regulation through chromatin alterations. However, the function of these motifs is still not clear. Studying ALL-1 presents an additional challenge because the gene is the human homologue of Drosophila trithorax. The latter is a member of the trithorax-Polycomb gene family which acts to determine the body pattern of Drosophila by maintaining expression or repression of the Antennapedia-bithorax homeotic gene complex. Here we apply yeast two hybrid methodology, in vivo immunoprecipitation and in vitro`pull down' techniques to show self association of the SET motifs of ALL-1, TRITHORAX and ASH1 proteins (Drosophila ASH1 is encoded by a trithoraxgroup gene). Point mutations in evolutionary conserved residues of TRITHORAX SET, abolish the interaction. SET ± SET interactions might act in integrating the activity of ALL-1 (TRX and ASH1) protein molecules, simultaneously positioned at di erent maintenance elements and directing expression of the same or di erent target genes. Oncogene (2000) 19, 351 ± 357.

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Section: Resultsmentioning

confidence: 99%

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

et al. 2000

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“…Whilst mammalian SUV39H1 was the first enzyme to be shown to possess HKMT activity towards H3K9 [19], its homolog, Su(var)3-9, in Drosophila was the first to be identified in a genetic screen for a suppressor of position effect variegation (PEV) [31]. The phenomenon of PEV was discovered by H. J. Muller in 1930 when describing the rearrangement of the white color eye gene from euchromatic to heterochromatic chromosomal regions.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of this conserved region in these two groups of proteins with opposing functions (maintaining gene repression by PcG and activation by trxG proteins) led to the proposition [41] that it may comprise a domain that interacts with common nucleic acid or protein targets for gene regulation. Later, Su(var)3-9 was found to contain the C-terminal domain that is also shared by E(Z) and Trx [31]. The SET domain is named after these three founding Drosophila proteins: Suppressor of variegation 3-9 [Su(var) [3][4][5][6][7][8][9], Enhancer of zeste [E(Z)], and Trithorax (Trx) [31].…”

Section: Introductionmentioning

confidence: 99%

Plant SET domain-containing proteins: Structure, function and regulation

Wang

Chandrasekharan

et al. 2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

170

195

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Modification of the histone proteins that form the core around which chromosomal DNA is looped has profound epigenetic effects on the accessibility of the associated DNA for transcription, replication and repair. The SET domain is now recognized as generally having methyltransferase activity targeted to specific lysine residues of histone H3 or H4. There is considerable sequence conservation within the SET domain and within its flanking regions. Previous reviews have shown that SET proteins from Arabidopsis and maize fall into five classes according to their sequence and domain architectures. These classes generally reflect specificity for a particular substrate. SET proteins from rice were found to fall into similar groupings, strengthening the merit of the approach taken. Two additional classes, VI and VII, were established that include proteins with truncated/ interrupted SET domains. Diverse mechanisms are involved in shaping the function and regulation of SET proteins. These include protein-protein interactions through both intra-and inter-molecular associations that are important in plant developmental processes, such as flowering time control and embryogenesis. Alternative splicing that can result in the generation of two to several different transcript isoforms is now known to be widespread. An exciting and tantalizing question is whether, or how, this alternative splicing affects gene function. For example, it is conceivable that one isoform may debilitate methyltransferase function whereas the other may enhance it, providing an opportunity for differential regulation. The review concludes with the speculation that modulation of SET protein function is mediated by antisense or sense-antisense RNA.

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“…Several E(var) and Su(var) proteins share distinctive motifs that are important for their ability to organize chromatin domains. The Su(var)3-9 protein and its mammalian ortholog SUV39H1 are unique in being the only characterized PEV modifiers that share two of these consensus motifs, the chromo and SET domains (1,50). Chromo domains are 40-amino-acid modular motifs that are implicated in protein self-association (8) and the assembly of site-specific multimeric complexes on chromatin (39,46).…”

mentioning

confidence: 99%

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

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Mammalian SET domain-containing proteins define a distinctive class of chromatin-associated factors that are targets for growth control signals and oncogenic activation. SUV39H1, a mammalian ortholog of Drosophila Su(var)3-9, contains both SET and chromo domains, signature motifs for proteins that contribute to epigenetic control of gene expression through effects on the regional organization of chromatin structure. In this report we demonstrate that SUV39H1 represses transcription in a transient transcriptional assay when tethered to DNA through the GAL4 DNA binding domain. Under these conditions, SUV39H1 displays features of a long-range repressor capable of acting over several kilobases to silence basal promoters. A possible role in chromatin-mediated gene silencing is supported by the localization of exogenously expressed SUV39H1 to nuclear bodies with morphologic features suggestive of heterochromatin in interphase cells. In addition, we show that SUV39H1 is phosphorylated specifically at the G 1 /S cell cycle transition and when forcibly expressed suppresses cell growth. Growth suppression as well as the ability of SUV39H1 to form nuclear bodies and silence transcription are antagonized by the oncogenic antiphosphatase Sbf1 that when hyperexpressed interacts with the SET domain and stabilizes the phosphorylated form of SUV39H1. These studies suggest a phosphorylation-dependent mechanism for regulating the chromatin organizing activity of a mammalian su(var) protein and implicate the SET domain as a gatekeeper motif that integrates upstream signaling pathways to epigenetic regulation and growth control.The formation and propagation of higher-order chromatin states are dynamic processes that establish distinct domains that are either permissive or restrictive for transcription. The functions of such domains have been implicated in the epigenetic control of developmental gene expression in Drosophila (38), proper sister chromatid segregation during meiosis (11), and telomeric and centromeric silencing in yeast (22,35). The molecular mechanisms that regulate these and other properties of higher-order chromatin are essentially unknown.Genetic analyses in Drosophila and yeast have identified several genes that participate in the formation of euchromatin or heterochromatin states. Some of these encode proteins that contribute to either an enhancement [E(var)] or suppression [Su(var)] of position effect variegation (PEV) (42). PEV is a gene silencing mechanism that results from the spreading of heterochromatin, thus implicating E(var) and Su(var) proteins in the formation of euchromatic and heterochromatic domains, respectively. Several E(var) and Su(var) proteins share distinctive motifs that are important for their ability to organize chromatin domains. The Su(var)3-9 protein and its mammalian ortholog SUV39H1 are unique in being the only characterized PEV modifiers that share two of these consensus motifs, the chromo and SET domains (1, 50). Chromo domains are 40-amino-acid modular motifs that are implicated in...

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The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes.

Cited by 520 publications

References 57 publications

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

Plant SET domain-containing proteins: Structure, function and regulation

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

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