Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes inDrosophilais mediated by the epigenetic chromatin modifiers
| Autor: | Angelina A. Akishina, B. A. Kuzin, Grigori Enikolopov, Alexander Mazo, Svetlana Petruk, I B Mertsalov, O. B. Simonova, Vladislav M. Panin, Mikhail S. Slezinger, R. O. Cherezov, Olga G. Zatsepina, Julia E. Vorontsova |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transgene xenobiotic PcG epigenetic complexes 03 medical and health sciences 0302 clinical medicine Transcription (biology) Epigenetics Gene Transcription factor Genetics biology aryl hydrocarbon receptor drosophila respiratory system Aryl hydrocarbon receptor respiratory tract diseases 3. Good health Chromatin Cell biology 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Signal transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.22173 |
| Popis: | // Angelina A. Akishina 1, * , Julia E. Vorontsova 1, * , Roman O. Cherezov 1 , Il’ya B. Mertsalov 1 , Olga G. Zatsepina 2 , Mikhail S. Slezinger 1 , Vladislav M. Panin 3 , Svetlana Petruk 4 , Grigori N. Enikolopov 5 , Alexander Mazo 4 , Olga B. Simonova 1 and Boris A. Kuzin 1 1 Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia 2 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 3 Department of Biochemistry and Biophysics, Texas AM aryl hydrocarbon receptor; PcG epigenetic complexes; drosophila Received: May 19, 2017 Accepted: October 13, 2017 Published: October 31, 2017 ABSTRACT Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR’s target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgenic Drosophila lines with an inducible human AhR gene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control proliferation, motility, polarization, and programmed cell death. This suggests that AHR activation may affect the expression of gene networks that could be critical for cancer progression and metastasis. Importantly, we found that AHR target genes are also controlled by the enzymes that modify chromatin structure, in particular components of the epigenetic Polycomb Repressive complexes 1 and 2. Since exogenous AHR ligands (alternatively – xenobiotics) and small molecule inhibitors of epigenetic modifiers are often used as pharmaceutical anticancer drugs, our findings may have significant implications in designing new combinations of therapeutic treatments for oncological diseases. |
| Databáze: | OpenAIRE |
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