Functional analysis of the chromo domain of HP1.

Platero, J. Suso; Hartnett, Thomas; Eissenberg, Joel C.

doi:10.1002/j.1460-2075.1995.tb00069.x

Cited by 261 publications

(246 citation statements)

References 38 publications

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“…Previous studies have demonstrated that chromo domain-containing proteins, including Su(var)3-9 and its orthologs, localize to regions of chromatin that are transcriptionally silenced (1,22,39). Our own subnuclear localization of SUV39H1 to electron-dense nuclear foci supports the notion that SUV39H1 may associate with transcriptionally inactive chromatin.…”

Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1supporting

confidence: 86%

“…The repressor property of SUV39H1 localized to its amino-terminal half which also contains a chromo domain, a modular motif that self-associates and assembles into multimeric complexes on chromatin (31,39,46). Notably, transcriptional repression by SUV39H1 did not require its SET domain.…”

Section: Discussionmentioning

confidence: 99%

“…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). SET domains are 130-amino-acid motifs named for three proteins in which they were originally identified: Su(var)3-9, Enhancer-of-zeste, and Trithorax (25).…”

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confidence: 99%

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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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Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1supporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…This domain shares > 70% sequence identity with protein in Drosophila and mouse [26]. Recently it was shown that the HP1 chromo domain has chromosome binding activity and that proteins with this domain are recruited to their distinct chromosomal binding sites, probably due to protein-protein interaction [36]. It is generally acknowledged that autoepitopes on nuclear antigens are conserved and functional domain regions [5,37,38].…”

Section: Discussionmentioning

confidence: 99%

Clinical features of anti-chromo antibodies associated with anti-centromere antibodies

Iwai

Muro

Sugimoto

et al. 1996

Clinical and Experimental Immunology

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SUMMARYAnti-chromo antibodies (AChA) are autoantibodies accompanying anti-centromere antibodies (ACA). We determined the frequency and clinical significance of AChA in autoimmune rheumatic diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and with recombinant N-terminus of 25-kD chromo protein (p25). AChA were detected in 28 (36%) of 77 sera with ACA. AChA were found only in ACA-positive sera. Twenty-two (79%) of 28 recognized a recombinant N-terminal portion of p25, including the chromo domain which is conserved among species. AChA were related to leucopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, and existence of Sjögren's syndrome (SS). In ACA-positive patients, AChA might be a serologic indicator of systemic sclerosis (SSc), having features of systemic lupus erythematosus and/or SS or diseases other than SSc.

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“…DNA was counterstained with propidium iodide after RNase treatment. Immunostaining of polytene chromosomes from salivary glands was done using a 1:100 dilution of anti-ASF1 antibody (Platero et al 1995).…”

Section: Immunostaining Techniquesmentioning

confidence: 99%

Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery

Moshkin¹,

Armstrong²,

Maeda³

et al. 2002

Genes Dev.

108

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De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophila asf1 gene derepress silencing at heterochromatin and that the ASF1 protein has a cell cycle-specific nuclear and cytoplasmic localization. Furthermore, using both genetic and biochemical methods, we demonstrate that ASF1 interacts with the Brahma (SWI/SNF) chromatin-remodelling complex. These findings suggest that ASF1 plays a crucial role in both chromatin assembly and SWI/SNF-mediated chromatin remodelling.

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Functional analysis of the chromo domain of HP1.

Cited by 261 publications

References 38 publications

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

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

Clinical features of anti-chromo antibodies associated with anti-centromere antibodies

Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery

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