The transcriptional response to androgens of the rat VCSA1 gene is amplified by both binary and graded mechanisms
The transcriptional response to androgens of the rat VCSA1 gene is amplified by both binary and graded mechanisms
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DOI：
10.1210/en.142.10.4550
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Rougeon, F
中科院分区：
文献类型：
--
作者：
Rosinski-Chupin, I;Huaulmé, JF;Rougeon, F
在高等真核生物中，基因表达可以因循环激素诱导剂的微小变化而发生高度改变。为了确定青春期大鼠颌下腺腺泡细胞中雄激素调节基因 VCSA1 表达增强 100 至 200 倍的机制，我们在单细胞水平上对 VCSA1 表达进行了详细分析。通过对成熟和初级 VCSA1 转录本的原位检测，我们发现，在青春期前和去势男性以及女性中，在循环雄激素水平较低的情况下，VCSA1 表达仅在一小部分分化的腺泡细胞中被激活。在雄性性成熟的过程中，我们发现表达 VCSA1 的腺泡细胞比例增加，并且阳性细胞群中 VCSA1 异质核 RNA 和 mRNA 含量增加。最后，我们发现 VCSA1 甲基化模式的变化与 VCSA1 转录激活相关。这些结果表明，雄激素在生理条件下可以引起二元反应和分级反应。他们还提供证据表明，在基础条件下大多数细胞中的转录抑制可能会扩大基因调控的范围。
In higher eukaryotes, gene expression can be highly modified in response to small variations of circulating hormonal inducers. To determine the mechanisms responsible for the 100- to 200-fold enhancement of expression of an androgen-regulated gene, VCSA1, in the acinar cells of rat submandibular glands during puberty, we performed a detailed analysis of VCSA1 expression at the single cell level. Using in situ detection of mature and primary VCSA1 transcripts, we show that VCSA1 expression is activated in only a small proportion of differentiated acinar cells in the presence of low levels of circulating androgens in prepubescent and in castrated males, as well as in females. During the time course of sexual maturation in males, we demonstrate an increase in the proportion of acinar cells expressing VCSA1 and an increase in VCSA1 heterogeneous nuclear RNA and mRNA content in the positive cell population. Finally, we show that changes in the methylation pattern of VCSA1 are correlated with VCSA1 transcriptional activation. These results demonstrate that androgens can, in physiological conditions, elicit both a binary and a graded response. They also provide evidence that the range of gene regulation may be expanded by a transcriptional repression in a majority of cells under basal conditions.