Abstract
To study the regulatory mechanism of the Aryl hydrocarbon receptor (AHR), target genes of transcription are necessary for understanding the normal developmental and pathological processes. Here, we examined the effects of human AHR ligands on male fecundity. To induce ectopic human AhR gene expression, we used Drosophila melanogaster transformed with human AhR under the control of a yeast UAS promoter element capable of activation in the two-component UAS-GAL4 system. We found that exogenous AHR ligands decrease the number of Drosophila gonadal Tj-positive cells. We also found both an increase and decrease of AHR target gene expression, including in genes that control homeostasis and testis development. This suggests that gonadal AHR activation may affect the expression of gene networks that control sperm production and could be critical for fertility not just in Drosophila but also in humans. Finally, we found that the activation of the expression for some AHR target genes depends on the expression of testis-specific chaperone CG5017 in gonadal cells. Since CG5017 belongs to the nucleosome assembly protein (NAP) family and may participate in epigenetic regulation, we propose that this nucleotropic chaperone is essential to provide the human AHR with access to only the defined set of its target genes during spermatogenesis.
Highlights
There is evidence that the Aryl hydrocarbon receptor (AHR) plays an important role in normal development and cancerogenesis [1,2,3,4,5,6,7,8,9,10,11,12,13,14]
Ligand binding is critical for AHR activation, because after the binding it moves to the nucleus, dimerizes with the Aryl hydrocarbon receptor nuclear translocator (ARNT), and starts functioning as a transcriptional factor which binds to specific DNA sequences known as the xenobiotic response elements (XRE), driving expression of its target genes [20,21]
Since CG5017 belongs to the nucleosome assembly protein (NAP) family [34] and may participate in epigenetic regulation, we proposed that this nucleotropic chaperone is essential to provide human AHR access to a defined set of its target genes in soma during spermatogenesis
Summary
There is evidence that the Aryl hydrocarbon receptor (AHR) plays an important role in normal development and cancerogenesis [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. The growth of the chemical and pharmaceutical industries has created conditions under which every person has a risk of exposure to xenobiotics This may result in a variety of activations of ectopic AHR target genes in different tissues and at different stages of development. For a better understanding of the function of human AHR in vivo, we created “humanized” Drosophila transgenic flies, which carry transgenes with the controlled expression of the human AhR gene guided by the yeast upstream activation sequence (UAS) [32] This transgenic construct permits the induction of human AHR expression in certain Drosophila organs and cells with the help of tissue-specific GAL4-driver lines expressing a yeast GAL4 activator capable of recognizing UAS sequences and driving the transcription of downstream genes [33]. Since CG5017 belongs to the nucleosome assembly protein (NAP) family [34] and may participate in epigenetic regulation, we proposed that this nucleotropic chaperone is essential to provide human AHR access to a defined set (but not all) of its target genes in soma during spermatogenesis
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