Tip60 Is a Cell-Type-Specific Transcriptional Regulator

Hlubek, Falk; Löhberg, Christian; Meiler, Jens; Jung, Andreas; Kirchner, Thomas; Brabletz, Thomas

doi:10.1093/oxfordjournals.jbchem.a002901

Cited by 50 publications

(47 citation statements)

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“…In contrast, an active repression mechanism has been proposed for ␦EF1 with respect to regulation of ␣ 4 integrin (41), and a repression domain close to the N terminus was identified as necessary for repression of the ␦-crystalline enhancer (42). Although no complex was identified biochemically, the human immunodeficiency virus, type 1, Tat-interacting protein TIP60 has recently been put forward as a corepressor for ␦EF1 in repressing CD4-enhancer/promoter activity (43). In overexpression studies, we can show an interaction between TIP60 and ␦EF1 but not SIP1 2 excluding TIP60 as a potential corepressor for SIP1.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin

Grunsven

Michiels

Putte

et al. 2003

Journal of Biological Chemistry

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␦EF1 and SIP1 (or Zfhx1a and Zfhx1b, respectively) are the only known members of the vertebrate Zfh1 family of homeodomain/zinc finger-containing proteins. Similar to other transcription factors, both Smad-interacting protein-1 (SIP1) and ␦EF1 are capable of repressing E-cadherin transcription through binding to the E2 boxes located in its promoter. In the case of ␦EF1, this repression has been proposed to occur via interaction with the corepressor C-terminal binding protein (CtBP). In this study, we show by coimmunoprecipitation that SIP1 and CtBP interact in vivo and that an isolated CtBP-binding SIP1 fragment depends on CtBP for transcriptional repression. However, and most importantly, full-length SIP1 and ␦EF1 proteins do not depend on their interaction with CtBP to repress transcription from the E-cadherin promoter. Furthermore, in E-cadherin-positive kidney epithelial cells, the conditional synthesis of mutant SIP1 that cannot bind to CtBP abrogates endogenous E-cadherin expression in a similar way as wild-type SIP1. Our results indicate that fulllength SIP1 can repress E-cadherin in a CtBP-independent manner.

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Section: Discussionmentioning

confidence: 99%

Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin

Grunsven

Michiels

Putte

et al. 2003

Journal of Biological Chemistry

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“…The extent of activation induced by Tip60 isoproteins is similar to that of GATA4 -6 and Nkx2.5, especially when the chromodomain is deleted from Tip60␤⌬c. Moreover the induction of ANF activation by SRF/Tip60 is similar to the extent of induction or repression of other promoters by Tip60 when partner-bound to human immunodeficiency virus-Tat (1), androgen receptor (5, 6), cAMP-response element-binding protein (8), zinc-finger E box binding protein (9), or STAT3 (10).…”

Section: Discussionmentioning

confidence: 78%

“…For example, Tip60 co-activates transcription with human immunodeficiency virus-1 Tat (1), androgen receptor (5,6), and ␤-amyloid precursor protein-Fe65 complex (7). By contrast, Tip60 co-represses transcription with cAMP-response element-binding protein (8), zinc finger E box binding protein (9), and STAT3 (10), which repression is potentiated by histone deacetylase 7 (HDAC7).…”

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confidence: 99%

Co-activation of Atrial Natriuretic Factor Promoter by Tip60 and Serum Response Factor

Kim

Merlo

Wilson

et al. 2006

Journal of Biological Chemistry

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Tat-interactive protein 60 (Tip60) is a member of the MYST family of histone acetyltransferases (HATs). In addition to its HAT domain, Tip contains a heterochromatin-associated protein 1-like chromodomain and a zinc finger-like domain. Several alternative splice variants of Tip60 have been characterized, including fulllength Tip60␣, Tip60␤ (which lacks exon V encoded by the Tip60 gene), and Tip55 (which encodes a novel 103-amino-acid C terminus). We report here that isoproteins recognized by a pan-Tip60 antibody are strongly and transiently expressed between embryonic days 8 and 11 in the embryonic mouse myocardium. A functional role for Tip60 isoproteins in cardiac myocyte differentiation is suggested by immunoprecipitation experiments showing that Tip60␣, Tip60␤, and Tip55 can bind serum response factor (SRF) and by transient transfection assessments showing that Tip60 and SRF cooperatively activate the atrial natriuretic factor promoter. Although this combinatorial activity is inhibited by histone deacetylase 7, it was unexpectedly enhanced by point mutation of the HAT domain. Ablation of the chromodomain from Tip60␤ caused derepression. These findings suggest that Tip60 modulates expression of SRF-dependent cardiac genes.Since its discovery in 1996 (1), numerous findings have established Tat-interactive protein 60 kDa (Tip60) 3 as a member of the "MYST" family, an acronym denoting the founding members MOZ, YBF2, SAS2, and Tip60 of the family. Although Tip60 proteins are essential for embryonic development as determined by very early embryolethality resulting from homozygous ablation of the Tip60 gene, 4 the cellular function of its alternatively spliced isoforms as well as of its functional domains is only beginning to be understood. Among possible functions, Tip60 has been implicated in chromatin-remodeling complexes wherein it is required for apoptosis and DNA repair (3), during which it mediates acetylation-dependent exchange of histone H2A.X (4). Several studies utilizing transient transfection analysis have implicated Tip60 in the regulation of gene transcription, although whether it functions as a co-activator or co-repressor appears to be context-dependent. For example, Tip60 co-activates transcription with human immunodeficiency virus-1 Tat (1), androgen receptor (5, 6), and ␤-amyloid precursor protein-Fe65 complex (7). By contrast, Tip60 co-represses transcription with cAMP-response element-binding protein (8), zinc finger E box binding protein (9), and STAT3 (10), which repression is potentiated by histone deacetylase 7 (HDAC7).Several putative functional domains are present in Tip60, all of which are atypical. These include a chromatin organization modifier domain (chromodomain), a zinc finger-like domain, and a histone acetyltransferase (HAT) domain. The HAT domain was recently shown to obligatorily acetylate nucleosomal histones during DNA repair (4); however whether Tip60-mediated histone acetylation is required during transcription is unclear. Little is known about the function of the other do...

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“…4e). Alternatively, Tip60 negatively regulates the gene expression by binding to signal transducers and activators of transcription 3 [30], cAMP response element-binding protein [31], and zinc finger E box-binding protein [32] which are all involved in tumor progression. Regulation of transcriptional factors by Tip60 may be a therapeutic approach for inhibition of tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway

Takino

Nakada

et al. 2015

Clin Exp Metastasis

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A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and remodeling chromatin. In addition to histone acetyltransferase activity, Tip60 is known to regulate a variety of cellular functions, including gene expression, DNA damage response, cell migration and apoptosis. Lower expression of Tip60 is observed in lymphomas, melanomas, breast, colon, and lung cancer. It is widely accepted that Tip60 functions as a tumor suppressor. However, a role of Tip60 in gliomas still remains unclear. In this study, we investigated the role of Tip60 in the malignant behavior of human gliomas. By quantitative RT-PCR analysis using fresh human brain tumor tissues from 55 patients, we found that lower Tip60 expression and higher membrane-type 1 matrix metalloproteinase (MT1-MMP) expression are associated with advanced tumor grade in glioma tissues. Knockdown of Tip60 in glioblastoma cells promoted cell adhesion, spreading and MT1-MMP transcription and thereby invasion, which was suppressed by inhibition of MT1-MMP and nuclear factor-kappa B (NF-κB) activity. We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells by suppressing NF-κB pathway.Abbreviations: ECM, extracellular matrix; HAT, histone acetyltransferase; HDAC, histone deacetylase; MT1-MMP, membrane-type 1 matrix metalloproteinase; NF-κB, nuclear factor-kappa B; PBS, phosphate-buffered saline; QRT-PCR, quantitative real-time-PCR; Tip60, Tat-interacting protein 60 kDa;

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Tip60 Is a Cell-Type-Specific Transcriptional Regulator

Cited by 50 publications

References 0 publications

Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin

Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin

Co-activation of Atrial Natriuretic Factor Promoter by Tip60 and Serum Response Factor

Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway

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