The histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes

Schnur, Nicole; Seuter, Sabine; Katryniok, Careen; Rådmark, Olof; Steinhilber, Dieter

doi:10.1016/j.bbalip.2007.08.003

Cited by 34 publications

(39 citation statements)

References 34 publications

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“…For the purpose of our studies, we used a promoter fragment (−778 to +53) of ALOX5 that was fused to a luciferase reporter gene. [9][10][11] In order to understand transcript initiation in more detail, we investigated the chromatin signatures at the endogenous promoter and observed that TSA treatment leads to a profound upregulation of the canonical H3K4me3 signature. Therefore, we started to investigate the function of the H3K4 histone methyltransferase MLL and its role in the control of ALOX5 transcription.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] Here we analyzed the TSAmediated induction of 5-LO mRNA expression in a timedependent manner in MM6 and HL-60 cells. Cells were grown in the presence or absence of TSA (330 nM) for the indicated time points (Figure 1a).…”

Section: Time-dependent Induction Of Alox5 Mrna Expression and Histonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…11 The status of histone acetylation, as a marker for active gene transcription, is regulated by histone acetyl transferases and counteracted by HDACs. 12 HDACs deacetylate histones as well as other proteins such as transcription factors and can be divided into different classes, namely class I (comprising HDACs 1, 2, 3, 8), class II (4, 5, 6, 7, 9, 10) and class IV (11). 13 In addition to acetylation, phosphorylation and ubiquitination, the methylation of histones at certain residues contributes to a sophisticated system called the 'histone code' that is directly linked to the regulation and transcriptional memory of cellular gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wildtype MLL

et al. 2015

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The ALOX5 gene encodes 5-lipoxygenase (5-LO), a key enzyme of inflammatory reactions, which is transcriptionally activated by trichostatin A (TSA). Physiologically, 5-LO expression is induced by calcitriol and/or transforming growth factor-β. Regulation of 5-LO mRNA involves promoter activation and elongation control within the 3′-portion of the ALOX5 gene. Here we focused on the ALOX5 promoter region. Transcriptional initiation was associated with an increase in histone H3 lysine 4 trimethylation in a TSA-inducible manner. Therefore, we investigated the effects of the MLL (mixed lineage leukemia) protein and its derivatives, MLL-AF4 and AF4-MLL, respectively. MLL-AF4 was able to enhance ALOX5 promoter activity by 47-fold, which was further stimulated when either vitamin D receptor and retinoid X receptor or SMAD3/SMAD4 were co-transfected. In addition, we investigated several histone deacetylase inhibitors (HDACi) in combination with gene knockdown experiments (HDAC1-3, MLL). We were able to demonstrate that a combined inhibition of HDAC1-3 induces ALOX5 promoter activity in an MLL-dependent manner. Surprisingly, a constitutive activation of ALOX5 by MLL-AF4 was inhibited by class I HDAC inhibitors, by relieving inhibitory functions deriving from MLL. Conversely, a knockdown of MLL increased the effects mediated by MLL-AF4. Thus, HDACi treatment seems to switch 'inactive MLL' into 'active MLL' and overwrites the dominant functions deriving from MLL-AF4.

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Section: Discussionmentioning

confidence: 99%

Section: Time-dependent Induction Of Alox5 Mrna Expression and Histonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wildtype MLL

et al. 2015

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“…On one hand, HDACi inhibited the activity of HDACs, which interact with sequence-specific transcriptional factors on p27 Kip1 promoter and deacetylate promoter-bound histones (21)(22)(23)(24)(25)(26)(27). Therefore NaB could directly inhibit the HDACs of the p27 Kip1 promoter to cause an accumulation of acetylated histones for the access of basal transcriptional factors to the promoter, such as activating the binding of SP1 to proximal GC boxes (22)(23)(24), NF-Y to the CCAAT box (24), ectopic E2F to 5'-TTTG/CG/ CCGC-3' sequences (25,28) and repressing the binding of c-Myc to Inr elements (27), NF-κB to 5'-GGGCTTCCCC-3' sequences (27). On the other hand, HDACi may indirectly block the pathway of AKT or ERK and affect the expression of c-Myc and FoxO factors which inhibited p27…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line

Chen

Feng²,

Xu³

et al. 2011

Int J Mol Med

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Abstract. Trastuzumab has efficacy to improve the effect of cytotoxic drugs, such as paclitaxel and anthracyclin, against HER2-overexpressing breast cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, is known to have antitumoral properties. However, whether and how trastuzumab possesses the potential to synergize the anti-tumor effect of NaB on breast cancer cells is still equivocal. To elucidate whether combined treatment with NaB and trastuzumab exerts antitumor effects on a HER2-overexpressing breast cancer cell line, SKBR3 cells were treated with NaB alone or in combination with trastuzumab, and the effects on proliferation and cell cycle progression were analyzed. Combinatory treatment with NaB (4 mmol/l) and trastuzumab (20 µg/ml) significantly increased the growth-inhibitory effect on SKBR3 breast cancer cells, in comparison to NaB or trastuzumab treatment alone. The growthinhibitory effect of the combination of NaB and trastuzumab was accompanied by elevated mRNA and protein levels of the cyclin-dependent kinase inhibitor p27 Kip1 . In contrast, this effect was absent in HER2-negative HCC1937 cells. In conclusion, trastuzumab significantly improved the antitumor effect of NaB on HER2-overexpressing breast cancer cell line in vitro.

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5-Lipoxygenase

Werz¹,

Rådmark²

2016

Lipoxygenases in Inflammation

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The histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes

Cited by 34 publications

References 34 publications

Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wildtype MLL

Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wildtype MLL

Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line

5-Lipoxygenase

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