Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str. 26, Moscow 119991, Russia.
Int J Mol Sci. 2018 Dec 29;20(1):118. doi: 10.3390/ijms20010118.
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 gene expression, we used transformed with human under the control of a yeast promoter element capable of activation in the two-component system. We found that exogenous AHR ligands decrease the number of 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 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 in gonadal cells. Since 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.
为了研究芳香烃受体（AHR）的调控机制，了解转录的靶基因对于理解正常的发育和病理过程是必要的。在这里，我们研究了人类 AHR 配体对雄性生育力的影响。为了诱导异位的人类基因表达，我们使用酵母双杂交系统中受酵母启动子元件控制的二聚体系统来转化，该启动子元件能够在二聚体系统中被激活。我们发现外源性 AHR 配体减少了 睾丸 Tj 阳性细胞的数量。我们还发现 AHR 靶基因表达的增加和减少，包括控制体内平衡和睾丸发育的基因。这表明睾丸 AHR 的激活可能会影响控制精子发生的基因网络的表达，这对于不仅仅是 而且对于人类的生育能力可能是至关重要的。最后，我们发现一些 AHR 靶基因表达的激活依赖于睾丸细胞中睾丸特异性伴侣蛋白 的表达。由于 属于核小体组装蛋白（NAP）家族，可能参与表观遗传调控，因此我们提出，这种核蛋白伴侣对于在精子发生过程中为人类 AHR 提供对其靶基因的特定子集的访问是必不可少的。
