Epigenetic Therapy: Novel Translational Implications for Arrest of Environmental Dioxin-Induced Disease in Females

Zaraq Khan, Khan Z, Ye Zheng, Zheng Y, Jones TL, T.L. Jones, Tiffanny L Jones, Abigail A. Delaney, Delaney AA, Correa LF, Luiz F. Correa, Chandra C. Shenoy, Khashayarsha Khazaie, Khazaie K, Gaurang S. Daftary, Daftary GS
Endocrinology · 2017 · vol. 159(1) , pp. 477–489 · doi:10.1210/en.2017-00860 · PMID:29165700 · W2768826621
Lab / animal OA: bronze CC0 ⤵ 6 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-10 ⓘ

This study demonstrates that an epigenetic histone acetyltransferase inhibitor can repress dioxin-induced gene expression and disease progression in endometrial cells and an animal model for endometriosis.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Increased toxicant exposure and resultant environmentally induced diseases are a tradeoff of industrial productivity. Dioxin [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)], a ubiquitous byproduct, is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome (CYP) p450 metabolic enzymes that alter organ function to cause disease. In contrast, the transcription factor, Krüppel-like factor (KLF) 11, represses these enzymes via epigenetic mechanisms. In this study, we characterized these opposing mechanisms in vitro and in vivo as well as determining potential translational implications of epigenetic inhibitor therapy. KLF11 antagonized TCDD-mediated activation of CYP3A4 gene expression and function in endometrial cells. The repression was pharmacologically replicated by selective use of an epigenetic histone acetyltransferase inhibitor (HATI). We further showed phenotypic relevance of this mechanism using an animal model for endometriosis. Fibrotic extent in TCDD-exposed wild-type animals was similar to that previously observed in Klf11-/- animals. When TCDD-exposed animals were treated with a HATI, Cyp3 messenger RNA levels and protein expression decreased along with disease progression. Fibrotic progression is ubiquitous in environmentally induced chronic, untreatable diseases; this report shows that relentless disease progression can be arrested through targeted epigenetic modulation of protective mechanisms.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Carcinogens, Environmental Endometriosis Endometrium Enzyme Inhibitors Epigenesis, Genetic Histone Acetyltransferases Polychlorinated Dibenzodioxins Animals Animals Apoptosis Regulatory Proteins Apoptosis Regulatory Proteins Carcinogens, Environmental Carcinogens, Environmental Carcinogens, Environmental Cell Line Cell Line Chromatin Immunoprecipitation Chromatin Immunoprecipitation Cytochrome P-450 CYP3A Cytochrome P-450 CYP3A

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (67)

Cited by (6)

Source provenance

europepmc
last seen: 2026-10-15T06:08:49.021275+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:20:57.725456+00:00
License: CC0 · commercial use OK