Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling Marks Critical for Transcriptional Activation

Schnekenburger, Michaël; Talaska, Glenn; Puga, Alvaro

doi:10.1128/mcb.00838-07

Cited by 135 publications

(105 citation statements)

References 55 publications

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“…TBQ, 1,2-NQ, and 1,4-NQ induced XRE-dependent luciferase activity (Fig. 4B), and binding of AhR and RNA pol II, which is one of the important factors to initiate transcription (Schnekenburger et al, 2007), to the Cyp1a1 enhancer region (−1.3 kbp) and proximal promoter region (−0.1 kbp) were also detected with TBQ and 1,2-NQ (Figs. 5A and 5B).…”

Section: Role Of Ahr In Cyp1a1 Induction By Mono-and Bi-aromatic Hydrmentioning

confidence: 96%

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Covalent binding of quinones activates the Ah receptor in Hepa1c1c7 cells

2015

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-Highly reactive quinone species produced by photooxidation and/or metabolic activation of mono-or bi-aromatic hydrocarbons modulate cellular homeostasis and electrophilic signal transduction pathways through the covalent modification of proteins. Polycyclic aromatic hydrocarbons, but not mono-or bi-aromatic hydrocarbons, are well recognized as ligands for the aryl hydrocarbon receptor (AhR). However, quinone species produced from mono-and bi-aromatic hydrocarbons could potentially cause AhR activation. To clarify the AhR response to mono-and bi-aromatic hydrocarbon quinones, we studied Cyp1a1 (cytochrome P450 1A1) induction and AhR activation by these quinones. We detected Cyp1a1 induction during treatment with quinones in Hepa1c1c7 cells, but not their parent compounds. Nine of the twelve quinones with covalent binding capability for proteins induced Cyp1a1. Cyp1a1 induction mediated by 1,2-naphthoquinone (1,2-NQ), 1,4-NQ, 1,4-benzoquinone (1,4-BQ) and tert-butyl-1,4-BQ was suppressed by a specific AhR inhibitor and was not observed in c35 cells, which do not have a functional AhR. These quinones stimulated AhR nuclear translocation and interaction with the AhR nuclear translocator. Interestingly, 1,2-NQ covalently modified AhR, which was detected by an immunoprecipitation assay using a specific antibody against 1,2-NQ, resulting in enhancement of xenobiotic responsive element (XRE)-derived luciferase activity and binding of AhR to the Cyp1a1 promoter region. While mono-and bi-aromatic hydrocarbons are generally believed to be poor ligands for AhR and hence unable to induce Cyp1a1, our study suggests that the quinones of these molecules are able to modify AhR and activate the AhR/XRE pathway, thereby inducing Cyp1a1. Since we previously reported that 1,2-NQ and tert-butyl-1,4-BQ also activate NF-E2-related factor 2, it seems likely that some of quinones are bi-functional inducers for phase-I and phase-II reaction of xenobiotics.

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Section: Role Of Ahr In Cyp1a1 Induction By Mono-and Bi-aromatic Hydrmentioning

confidence: 96%

“…The ChIP assay was performed, with a minor modification, according to procedures described previously (Schnekenburger et al, 2007). Briefly, the cells were seeded in 15 cm dishes, incubated for 24 hr, and then incubated for a further 24 hr in serum-free medium.…”

Section: Chip Assaymentioning

confidence: 99%

Covalent binding of quinones activates the Ah receptor in Hepa1c1c7 cells

2015

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“…ChIP was performed with minor modifications of procedures described previously (Schnekenburger et al, 2007b). Chromatin from formaldehyde crosslinked Hepa-1 cells treated for 90 min with 5 nM TCDD or DMSO vehicle were sheared to a size range of 0.3-0.6 kb by sonication in a crushed-ice/ water bath with six 30-s bursts of 200 W, with a 30-s interval between bursts using a Bioruptor (Diagenode, Sparta, NJ).…”

Section: Chromatin Immunoprecipitation (Chip) Analysesmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

Marlowe

Fan

Chang

et al. 2008

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Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr ؊/؊ fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, ␥H2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RBnegative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G 0 /G 1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. INTRODUCTIONMembers of the E2F family of transcription factors are critical regulators of the G 1 /S phase transition of the cell cycle, during which their transcriptional activity is generally controlled through interaction with retinoblastoma (RB) family proteins. In addition, E2F proteins have functions beyond the G 1 /S phase transition that impact cell proliferation in a variety of ways (Dimova and Dyson, 2005). The E2F family consists of six extensively characterized and three less wellstudied members. E2F1, -2, and -3a are potent activators of transcription, bind exclusively to RB-p105, and are cyclically expressed during the cell cycle. E2F3b and -4, which can interact with RB-p107 and -p130, and E2F5, which binds only to p130, are poor transcriptional activators, and they function mainly as repressors through their recruitment of RB proteins to E2F-regulated promoters (Dyson, 1998;Nevins, 1998;DeGregori and Johnson, 2006). In general, the E2Fs with transactivator activity promote cell cycle progression, whereas the E2Fs with transrepressor activity function in cell cycle exit and differentiation (Dimova and Dyson, 2005). E2F6-8 are distinct from the other E2F members, lacking the transactivation and RB-binding domains, and they repress transcription in an RB-independent manner (Frolov and Dyson, 2004;DeGregori and Johnson, 2006).The best-characterized function of E2F ...

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“…Epigenetics entails the study of heritable changes in gene expression that occur independent of modifications to 89 nucleotide sequences (Schnekenburger M 2007 …”

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confidence: 99%