Cytokine-induced changes in chromatin structure and in vivo footprints in the inducible NOS promoter

Mellott, Jane K.; Nick, Harry S.; Waters, Michael F.; Billiar, T.R.; Geller, David A.; Chesrown, Sarah E.

doi:10.1152/ajplung.2001.280.3.l390

Cited by 30 publications

(26 citation statements)

References 38 publications

(47 reference statements)

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“…DNase I Hypersensitivity-DNase I hypersensitivity assays were performed as described previously (48). Briefly, HK-2 cells were treated with hemin (5 M) or vehicle (Me 2 SO) for 2 h. Cells were collected and nuclei isolated.…”

Section: Methodsmentioning

confidence: 99%

JunB and JunD Regulate Human Heme Oxygenase-1 Gene Expression in Renal Epithelial Cells

Hock

Liby

Wright

et al. 2007

Journal of Biological Chemistry

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Heme oxygenase-1 is a highly inducible gene, the product of which catalyzes breakdown of the prooxidant heme. The purpose of this study was to investigate the regulation of the human heme oxygenase-1 gene in renal epithelial cells. DNase I hypersensitivity studies identified three distal sites (HS-2, -3, and -4) corresponding to approximately ؊4.0, ؊7.2, and ؊9.2 kb, respectively, of the heme oxygenase-1 promoter in addition to one proximal region, HS-1, which we have shown previously to be an E box. In vivo dimethyl sulfate footprinting of the HS-2 region revealed six individual protected guanines. Two mutations within HS-2 combined with a third mutation of the proximal E box abolished hemin-and cadmium-driven heme oxygenase-1 promoter activation, suggesting that these three sites synergized for maximal heme oxygenase-1 induction. Jun proteins bound to the antioxidant response element in the HS-2 region in vitro and associated with the heme oxygenase-1 promoter in vivo. JunB and JunD contribute opposing effects; JunB activated whereas JunD repressed heme oxygenase-1 expression in human renal epithelial cells, results that were corroborated in junB ؊/؊ and junD ؊/؊ cells. We propose that heme oxygenase-1 induction is controlled by a dynamic interplay of regulatory proteins, and we provide new insights into the molecular control of the human heme oxygenase-1 gene.

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Section: Methodsmentioning

confidence: 99%

JunB and JunD Regulate Human Heme Oxygenase-1 Gene Expression in Renal Epithelial Cells

Hock

Liby

Wright

et al. 2007

Journal of Biological Chemistry

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“…In diabetic vascular disease, altered histone modifications may mediate the metabolic changes and proinflammatory alterations in SMCs (132). Not only is cytokine expression under epigenetic control, but cytokines themselves also induce (indirect) changes to the chromatin, providing an essential link between inflammation and epigenetic programming (89).…”

Section: Histone Modificationmentioning

confidence: 99%

The Role of Redox Signaling in Epigenetics and Cardiovascular Disease

Kim

Ryan²,

Archer³

2013

Antioxidants & Redox Signaling

108

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Significance: The term epigenetics refers to the changes in the phenotype and gene expression that occur without alterations in the DNA sequence. There is a rapidly growing body of evidence that epigenetic modifications are involved in the pathological mechanisms of many cardiovascular diseases (CVDs), which intersect with many of the pathways involved in oxidative stress. Recent Advances: Most studies relating epigenetics and human pathologies have focused on cancer. There has been a limited study of epigenetic mechanisms in CVDs. Although CVDs have multiple established genetic and environmental risk factors, these explain only a portion of the total CVD risk. The epigenetic perspective is beginning to shed new light on how the environment influences gene expression and disease susceptibility in CVDs. Known epigenetic changes contributing to CVD include hypomethylation in proliferating vascular smooth muscle cells in atherosclerosis, changes in estrogen receptor-a (ER-a) and ER-b methylation in vascular disease, decreased superoxide dismutase 2 expression in pulmonary hypertension (PH), as well as trimethylation of histones H3K4 and H3K9 in congestive heart failure. Critical Issues: In this review, we discuss the epigenetic modifications in CVDs, including atherosclerosis, congestive heart failure, hypertension, and PH, with a focus on altered redox signaling. Future Directions: As advances in both the methodology and technology accelerate the study of epigenetic modifications, the critical role they play in CVD is beginning to emerge. A fundamental question in the field of epigenetics is to understand the biochemical mechanisms underlying reactive oxygen species-dependent regulation of epigenetic modification.

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“…Cell permeabilization, DNase I treatment, and Southern analysis were performed as previously described ( 37,38 ). Following DNase I treatment, cell lysates were incubated overnight at 50°C, and genomic DNA was isolated by organic extraction, alcohol precipitation, and resuspension in TE.…”

Section: Dnase I Hypersensitive (Hs) Site and Southern Blot Analysismentioning

confidence: 99%

“…1 ) illustrate a constitutive DNase I HS site at ‫ف‬ 9.0-10 kb upstream of the transcriptional start site. We have previously shown that constitutive HS sites harbor specifi c inducible elements ( 37,45 ); therefore, we chose to further analyze this region.…”

Section: ␣ Enhancermentioning

confidence: 99%