Interaction of SP100 with HP1 proteins: A link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment

Seeler, Jacob-S.; Marchio, Agnès; Sitterlin, Delphine; Transy, Catherine; Dejean, Anne

doi:10.1073/pnas.95.13.7316

Cited by 247 publications

(250 citation statements)

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“…In these studies, increasing SP100 concentration in the presence of ETS1 proportionately decreased ETS1 transcriptional activity. SP100 has been shown to interact with heterochromatin protein 1 (HP1), which functions as a transcriptional repressor (Seeler et al, 1998), and SP100 acts as repressor of transcription when tethered to DNA (Lehming et al, 1998;Seeler et al, 1998;Bloch et al, 1999). However, SP100 and ETS1 have recently been reported to coactivate the MMP3 (stromelysin) promoter as well as a heterologous promoter containing multimerized EBS (Wasylyk et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…SP100 was first identified as a nuclear autoantigen in patients with the autoimmune disease Primary Biliary Cirrhosis (Szostecki et al, 1990, and its mRNA and protein is potently induced by interferon (IFN) . SP100 is a constituent member of the nuclear body (NB), a subnuclear organelle, also referred to as Kr-bodies, nuclear domain 10 (ND10) or PML oncogenic domains (PODs) (Lamond and Earnshaw, 1998;Seeler et al, 1998;Seeler and Dejean, 1999). The function of SP100, as well as NBs, remains unknown, although nuclear bodies have been implicated in the development of neoplasia and the progression of viral infection (Lamond and Earnshaw, 1998;Seeler et al, 1998;Seeler and Dejean, 1999).…”

Section: Introductionmentioning

confidence: 99%

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SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Yordy

Sementchenko

et al. 2004

Oncogene

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The ETS1 transcription factor is a member of the Ets family of conserved sequence-specific DNA-binding proteins. ETS1 has been shown to play important roles in various cellular processes such as proliferation, differentiation, lymphoid development, motility, invasion and angiogenesis. These diverse roles of ETS1 are likely to be dependent on specific protein interactions. To identify proteins that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we describe the functional interaction between SP100 and ETS1. SP100 protein interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear bodies and ETS1 expression alters the nuclear body morphology in living cells. SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA promoters in a dose-dependent manner, decreases the expression of these endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the invasion of breast cancer cells and is induced by Interferon-a, which has been shown to inhibit the invasion of cancer cells. These data demonstrate that SP100 modulates ETS1-dependent biological processes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Yordy

Sementchenko

et al. 2004

Oncogene

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“…24 In addition, SP100 can be covalently modified by the ubiquitinlike SUMO-1 protein. Since the SUMO-1 and ubiquitin proteins target the same lysines, it has been suggested that sumoylation of proteins antagonizes their ubiquitination, and thus protects them from ubiquitin-mediated degradation.…”

Section: Discussionmentioning

confidence: 99%

“…First, we determined the subcellular distribution of SP100 that interacts directly with HP1a protein. 24 The G2 cells from ICF patients were immunostained with an anti-SP100 antibody and showed that a high proportion of nuclei have a prominent bright SP100 focus, in addition to a diffuse faint staining of the nucleoplasm. Double immunocytochemistry with differently labelled HP1a and SP100 antibodies clearly demonstrated their perfect nuclear co-localization to the bright focus (Figure 6a).…”

Section: Aberrant Nuclear Distribution Of Hp1a Hp1b and Hp1c Proteinmentioning

confidence: 99%

Subcellular distribution of HP1 proteins is altered in ICF syndrome

et al. 2004

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The Immunodeficiency, Centromeric instability, and Facial (ICF) syndrome is a rare autosomal recessive disorder that results from mutations in the DNMT3B gene, encoding a DNA-methyltransferase that acts on GC-rich satellite DNAs. This syndrome is characterized by immunodeficiency, facial dysmorphy, mental retardation of variable severity and chromosomal abnormalities that essentially involve juxtacentromeric heterochromatin of chromosomes 1 and 16. These abnormalities demonstrate that hypomethylation of satellite DNA can induce alterations in the structure of heterochromatin. In order to investigate the effect of DNA hypomethylation on heterochromatin organization, we analyzed the in vivo distribution of HP1 proteins, essential components of heterochromatin, in three ICF patients. We observed that, in a large proportion of ICF G2 nuclei, all HP1 isoforms show an aberrant signal concentrated into a prominent bright focus that co-localizes with the undercondensed 1qh or 16qh heterochromatin. We found that SP100, SUMO-1 and other proteins from the promyelocytic leukemia nuclear bodies (NBs) form a large body that co-localizes with the HP1 signal. This is the first description of altered nuclear distribution of HP1 proteins in the constitutional ICF syndrome. Our results show that satellite DNA hypomethylation does not prevent HP1 proteins from associating with heterochromatin. They suggest that, at G2 phase, HP1 proteins are involved in the heterochromatin condensation and may therefore remain concentrated at these sites until the condensation is complete. They also indicate that proteins from the NB could play a role in this process. Finally, satellite DNA length polymorphism could affect the efficiency of heterochromatin condensation and thus contribute to the variability of the ICF phenotype.

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“…Remarkably, simultaneous expression of PML inhibits the repressive activity of Daxx, possibly by localizing it to the PODs (Lehembre et al, 2001;Li et al, 2000a). Another PODassociated protein, Sp100 (Szostecki et al, 1990), also represses transcription when fused to the Gal4 DBD and contains a heterochromatin1 (HP1) binding domain (Lehming et al, 1998;Seeler et al, 1998). The interaction of Sp100 and HP1 proteins was taken as a mechanistic explanation as to how Sp100 mediates transcriptional repression, i.e.…”

Section: Pml Pods and Transcriptional Regulationmentioning

confidence: 99%