AUTOREGULATION OF PIT-1 GENE-EXPRESSION MEDIATED BY 2 CIS-ACTIVE PROMOTER ELEMENTS
AUTOREGULATION OF PIT-1 GENE-EXPRESSION MEDIATED BY 2 CIS-ACTIVE PROMOTER ELEMENTS
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DOI：
10.1038/346583a0
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发表时间：
1990-08-09
期刊：
影响因子：
64.8
通讯作者：
ROSENFELD, MG
中科院分区：
文献类型：
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作者：
CHEN, RP;INGRAHAM, HA;ROSENFELD, MG
THEpit-1基因是编码参与发育的蛋白质的大家族的一员，该蛋白质包含高度同源的区域，称为POU结构域1 -9。Pit-1是一种垂体特异性转录因子，可激活生长激素和催乳素启动子的转录1，10。它在垂体前叶的成熟促甲状腺细胞、促生长细胞和促乳细胞类型中表达11，12，这些细胞类型在发育过程中依次出现;分别分泌生长激素和催乳素的促生长细胞和促乳细胞是最后出现的13。有趣的是，在个体发育过程中，在大鼠神经管和神经板（胚胎第10-11天）中观察到pit-1转录物，此后（第13天）消失，仅在催乳素和生长激素激活前仅在脑垂体前叶（第15天）重新出现12，14，15。这种双相模式表明pit-1基因表达的初始激活的复杂机制。在体外使用野生型和突变型启动子的转录和转染分析表明，Pit-1可以积极地自动调节pit-1启动子的表达，作为结合两个Pit-1结合元件的结果。5'端Pit-1结合位点的突变消除了正性自身调节，而紧邻帽位点3'端的元件的突变显著增加了pit-1启动子的表达。这些数据是一致的，积极的，衰减的自动调节环，似乎在pitlingpit-1基因表达的功能。
THEpit-1gene is a member of a large family of genes that encode proteins which are involved in development and which contain a highly homologous region, referred to as the POU domain1–9. Pit-1, a pituitary-specific transcription factor, can activate the transcription of the growth hormone and prolactin promoters1,10. It is expressed in mature thyrotroph, somatotroph and lactotroph cell types11,12of the anterior pituitary which arise sequentially during development; somatotrophs and lactotrophs, which secrete growth hormone and prolactin, respectively, are the last to arise13. Intriguingly, during ontogeny,pit-1transcripts are observed in the rat neural tube and neural plate (embryonic day 10–11) and disappear thereafter (day 13), only to reappear exclusively in the anterior lobe of the pituitary gland (day 15) just before activation of prolactin and growth hormone12,14,15. This biphasic pattern suggests a complex mechanism of initial activation ofpit-1gene expression. Transcription and transfection analysesin vitrousing wild-type and mutated promoters indicate that Pit-1 can positively autoregulate the expression of thepit-1promoter as a consequence of binding to two Pit-1-binding elements. Mutation of the 5' Pit-1-binding site abolished positive autoregulation, whereas mutation of the element located immediately 3' of the cap site markedly increased expression of thepit-1promoter. These data are consistent with a positive, attenuated autoregulatory loop that seems to function in maintainingpit-1gene expression.