NAP Family CG5017 Chaperone Pleiotropically Regulates Human AHR Target Genes Expression in Drosophila Testis

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.

Aryl Hydrocarbon Receptor as a Target for Lycopene Preventing DEHP-Induced Spermatogenic Disorders

“…84 A study indicated that AHR activation in the gonads could influence the expression of gene networks that control sperm production and may be of importance for fertility. 85 In addition, our study provided new findings that LYC prevented DEHP-induced spermatogenesis disturbance via AHR/ARNT signaling system, which might be the target molecule for future DEHP toxicity and LYC effector mechanism (Figure 8). In summary, our study indicated that LYC was conducive to improve sperm parameters such as reducing the levels of nuclear damage to DNA and deformity rate and increasing the values of sperm motility, number, and density.…”

“…It has been reported that AHR overexpression was found in Sertoli, Leydig, and spermatid cells of infertile subjects . A study indicated that AHR activation in the gonads could influence the expression of gene networks that control sperm production and may be of importance for fertility . In addition, our study provided new findings that LYC prevented DEHP-induced spermatogenesis disturbance via AHR/ARNT signaling system, which might be the target molecule for future DEHP toxicity and LYC effector mechanism (Figure ).…”