DEVELOPMENTAL SWITCH OF CREM - FUNCTION DURING SPERMATOGENESIS - FROM ANTAGONIST TO ACTIVATOR
DEVELOPMENTAL SWITCH OF CREM - FUNCTION DURING SPERMATOGENESIS - FROM ANTAGONIST TO ACTIVATOR
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DOI：
10.1038/355080a0
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发表时间：
1992-01-02
期刊：
影响因子：
64.8
通讯作者：
SASSONECORSI, P
中科院分区：
文献类型：
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作者：
FOULKES, NS;MELLSTROM, B;SASSONECORSI, P
哺乳动物精子发生由一系列由垂体-下丘脑轴控制的复杂发育过程组成 1. 这种生化信息流直接受腺苷酸环化酶信号转导途径调节 2. 我们之前描述了 CREM（环 AMP 反应元件调节剂）基因，该基因通过细胞特异性剪接产生 cAMP 转录反应的替代拮抗剂 3. 在这里，我们报告了一种新型 CREM 亚型的表达(CREM-tau) 存在于成人睾丸中。 CREM-tau 与之前表征的 CREM 拮抗剂不同，它协调插入了两个富含谷氨酰胺的结构域，赋予转录激活功能。在精子发生过程中，CREM 表达发生了突然的转变。在减数分裂前生殖细胞中，CREM 以拮抗剂形式少量表达。随后，从粗线期精母细胞阶段开始，剪接事件专门产生 CREM-tau 激活剂，并以极高的量积累。 CREM 功能中这种剪接依赖性逆转代表了基因表达发育调节的一个重要例子。
MAMMALIAN spermatogenesis consists of a series of complex developmental processes controlled by the pituitary-hypothalamic axis 1. This flow of biochemical information is directly regulated by the adenylate cyclase signal transduction pathway 2. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response 3. Here we report the expression of a novel CREM isoform (CREM-tau) in adult testis. CREM-tau differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREM-tau activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.