Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

Rösl, Frank; Dürst, Matthias; Hausen, Harald zur

doi:10.1002/j.1460-2075.1988.tb02947.x

Cited by 73 publications

(34 citation statements)

References 54 publications

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“…To check RNA quality, 5 g of RNA was separated on 1% agarose gels in the presence of ethidium bromide under non-denaturing conditions (36). For RT 1-3 g of RNA was mixed with 0.2 g of random primers (Roche), heated at 70°C for 10 min, and chilled on ice.…”

Section: Rna Analysis and Reverse Transcriptase (Rt)-pcr-cytoplasmicmentioning

confidence: 99%

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Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells

Riggelen¹,

Buchwalter²,

Soto³

et al. 2005

Journal of Biological Chemistry

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We have investigated the expression of c-fos in cervical carcinoma cells and in somatic cell hybrids derived therefrom. In malignant cells, c-fos was constitutively expressed even after serum starvation. Dissection of the c-fos promoter showed that expression was mainly controlled by the SRE motif, which was active in malignant cells, but repressed in their non-malignant counterparts. Constitutive SRE activity was not mediated by sustained mitogen-activated protein kinase activity but because of inefficient expression of the ternary complex factor Net, which was either very low or even barely discernible. Chromatin immunoprecipitation assays re-

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Section: Rna Analysis and Reverse Transcriptase (Rt)-pcr-cytoplasmicmentioning

confidence: 99%

“…This allows the examination of AP-1 in a cellular environment harboring identical viral transcription cassettes (36), but where the oncoproteins are expressed in a different genetic background (35). As depicted in Fig.…”

Section: Inverse Correlation Of C-fos and Fra-1 Expression In Tumorigmentioning

confidence: 99%

Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells

Riggelen¹,

Buchwalter²,

Soto³

et al. 2005

Journal of Biological Chemistry

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“…For instance, hepatic differentiation can be induced by 5-AzaC in rat fetuses (Rothrock et al, 19881, and fetal hemoglobin expression can be induced by this drug in adult baboons (Constantoulakis et al, 1989). The effects of 5-AzaC have also been demonstrated with studies of many other genes in various cell types, including marrow stromal cells (Andrews et al, 19891, HL-60 cells (Kong et al, 1991), fibroblasts (Chiang, 19811, and many transformed cells (Robert et al, 1988;Rosl et al, 1988;Avedimento et al, 1989;Rimoldi et al, 1991). More direct evidence has come from sequencing of a particular genomic DNA fragment (Church and Gilbert, 1984;Slauz et al, 1986).…”

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confidence: 90%

Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Wei

Lee

1994

Developmental Dynamics

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The mouse cellular retinoic acid binding protein-I (CRABP-I) gene is specifically up-regulated by retinoic acid (RA) in P19 mouse embryonal carcinoma cells, and its expression in animals is spatially and temporally restricted to RA-sensitive tissues during embryonic development. This study demonstrates that, in adult mouse tissues and P19 cells where the expression of CRABP-I is detected at the basal level, the 5'-flanking region of the CRABP-I gene is hypermethylated at the C residues of all the H p a I1 sites. Conversely, in mouse embryos during early stages of development when the expression of CRABP-I gene is detected at a much higher level, this region is demethylated at these H p a I1 sites. In P19, enhancement on the RA-induced up-regulation of CRABP-I can be observed in cells treated with 5-azacytidine (5-AzaC) in conjunction with RA, where partial demethylation in the 5'-flanking region of CRABP-I gene is observed. Nuclear run-on experiments indicate that increased message levels of CRABP-I in P19 cells can be accounted for, at least partially, by increases in its transcription rates. The induction of retinoic acid receptor (RAR) p by RA can also be enhanced by 5-AzaC, but to a much lesser degree. In contrast, all the H p a I1 sites in the structural gene portion, at least in the first two exons, are fully demethylated at the C residues. o 1994 WiIey-Liss, Inc.

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“…Moreover, inhibition of DNA methylation and histone deacetylation has been shown to promote keratinocyte differentiation (Rosl et al, 1988;Schmidt et al, 1989;Staiano-Coico et al, 1989), and an inverse correlation between DNA methylation and the expression of differentiating genes has been demonstrated in human keratinocytes (Engelkamp et al, 1993;Elder and Zhao, 2002). It has also been suggested that inhibition of differentiation by AEA occurs through changes in chromatin methylation patterns (Paradisi et al, 2008;Pasquariello et al, 2009), and that AEA induces DNA methylation of keratinocyte-differentiating genes by increasing DNA methyltransferase (DNMT) activity via a CB 1-dependent involvement of p38 and p42/p44 MAPK (Paradisi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic control of skin differentiation genes by phytocannabinoids

Pucci

Rapino

Francesco

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEEndocannabinoid signalling has been shown to have a role in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we investigated the possible epigenetic regulation of these genes by several phytocannabinoids, plant-derived cannabinoids that have the potential to be novel therapeutics for various human diseases. EXPERIMENTAL APPROACHThe effects of cannabidiol, cannabigerol and cannabidivarin on the expression of skin differentiation genes keratins 1 and 10, involucrin and transglutaminase 5, as well as on DNA methylation of keratin 10 gene, were investigated in human keratinocytes (HaCaT cells). The effects of these phytocannabinoids on global DNA methylation and the activity and expression of four major DNA methyltransferases (DNMT1, 3a, 3b and 3L) were also examined. KEY RESULTSCannabidiol and cannabigerol significantly reduced the expression of all the genes tested in differentiated HaCaT cells, by increasing DNA methylation of keratin 10 gene, but cannabidivarin was ineffective. Remarkably, cannabidiol reduced keratin 10 mRNA through a type-1 cannabinoid (CB1) receptor-dependent mechanism, whereas cannabigerol did not affect either CB1 or CB2 receptors of HaCaT cells. In addition, cannabidiol, but not cannabigerol, increased global DNA methylation levels by selectively enhancing DNMT1 expression, without affecting DNMT 3a, 3b or 3L. CONCLUSIONS AND IMPLICATIONSThese findings show that the phytocannabinoids cannabidiol and cannabigerol are transcriptional repressors that can control cell proliferation and differentiation. This indicates that they (especially cannabidiol) have the potential to be lead compounds for the development of novel therapeutics for skin diseases. AbbreviationsAEA, anandamide; 2-AG, 2-arachidonoylglycerol; CB1, cannabinoid receptor type I; CB2, cannabinoid receptor type II; CBD, cannabidiol; CBDV, cannabidivarin; CBG, cannabigerol; CPZ, capsazepine; DAGL, diacylglycerol lipase; DNMT, DNA methyltransferase; eCBs, endocannabinoids; ECS, endocannabinoid system; FAAH, fatty acid amide hydrolase; K1, keratin 1; K10, keratin 10; NAPE-PLD, N-acyl-phosphatidylethanolamines-specific phospholipase D; NHEK, normal human epidermal keratinocytes; MAGL, monoacylglycerol lipase; SR141716, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide; SR144528, N-[(1)-endo-1,3,3-trimethy-1-bicyclo [2.2.1]-heptan-2-yl]5-(4-chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-pyrazole-3-carboxamide; TGase 5, transglutaminase 5; THC, Δ 9-tetrahydrocannbinol; TPA, 12-O-tetradecanoylphorbol 13-acetate; TRPV1, transient receptor potential vanilloid 1 IntroductionEndocannabinoids (eCBs) are lipid mediators derived from membrane precursors and are involved in multiple regulatory functions, both in health and disease (Di Marzo and Petrosino, 2007). The two most important eCBs are N-arachidonylethanolamine ('anandamide', AEA) and 2-arachidonoylglycerol (2-AG) that elicit their a...

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Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

Cited by 73 publications

References 54 publications

Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells

Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells

Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Epigenetic control of skin differentiation genes by phytocannabinoids

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