Tissue-specific transcription start site usage in the leader exons of the rat insulin-like growth factor-I gene: evidence for differential regulation in the developing kidney.
Tissue-specific transcription start site usage in the leader exons of the rat insulin-like growth factor-I gene: evidence for differential regulation in the developing kidney.
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大鼠胰岛素样生长因子-I 基因前导外显子中的组织特异性转录起始位点使用：发育中肾脏差异调节的证据。
作者：
Joshua Shemer;M. Adamo;Charles T. Roberts;D. Leroith
肝外组织中胰岛素样生长因子- i （IGF-I）的产生支持自分泌和旁分泌功能，其调节方式与支持内分泌功能的肝脏不同。在大鼠肝脏中，转录起始主要发生在IGF-I基因外显子1上四个不同的、广泛分离的位点上，而在外显子2上，转录起始发生在一簇位点上。为了了解igf - 1基因表达的组织特异性调控的分子基础，我们绘制了以下肝外组织的转录起始位点使用图谱：睾丸、肺、肾、心脏、脑、肌肉和胃，并以肝脏作为对照。在成年大鼠中，肾脏和大脑表现出与肝脏相似的外显子1转录模式，即大致相同地使用起始位点2和3。相比之下，睾丸和肺优先使用3号起始点，胃、心脏和肌肉主要使用3号起始点。起始位点1和4在所有组织中都有极低水平的使用。在所研究的外显子2转录本表达的组织（睾丸、肺、胃和肾）中，外显子2转录启动模式与成年大鼠肝脏中的模式相同。在出生后发育过程中，肺和胃的外显子1和2的所有转录起始位点的使用是协调的。另一方面，肾脏中转录起始位点的选择在出生后发育过程中受到调控。具体来说，在外显子1中，起始位点3在出生前后的发育过程中都有组成性表达。相比之下，起始位点2的使用在胎儿晚期或出生后早期未被检测到，但仅在断奶阶段出现并迅速增加。肾脏的外显子2转录本也直到出生后才出现。这些数据表明，组织特异性和发育调节的转录因子调节IGF-I启动子活性，或者，由于使用不同的转录起始位点，组织特异性和发育阶段依赖性的IGF-I mrna的稳定性差异。这些不同的mrna可能在IGF-I产生的自分泌或旁分泌功能的差异调节中具有重要意义。
The production of insulin-like growth factor-I (IGF-I) in extrahepatic tissues supports both autocrine and paracrine functions and is regulated differently from that in liver, which supports endocrine function. In rat liver, transcription initiation primarily occurs at four distinct, widely separated sites in exon 1 of the IGF-I gene, whereas in exon 2, transcription initiation occurs at a cluster of sites. To understand the molecular basis for tissue-specific regulation of IGF-I gene expression, we have mapped transcription start site usage in the following extrahepatic tissues: testes, lung, kidney, heart, brain, muscle, and stomach, with liver serving as a control. In adult rats, kidney and brain exhibited a pattern of exon 1 transcription similar to that seen in liver, i.e. roughly equivalent use of start sites 2 and 3. In contrast, testes and lung preferentially used start site 3, while stomach, heart, and muscle predominantly used start site 3. Start sites 1 and 4 were used in all tissues at extremely low levels. In those tissues studied in which exon 2 transcripts are expressed (testes, lung, stomach, and kidney), the pattern of exon 2 transcription initiation was identical to that in adult rat liver. During postnatal development, the use of all transcription start sites in exons 1 and 2 was coordinate in lung and stomach. Selection of transcription start sites in the kidney, on the other hand, was subject to regulation during postnatal development. Specifically, within exon 1, start site 3 was expressed constitutively throughout peri- and postnatal development. In contrast, the usage of start site 2 was not detected at late fetal or early postnatal stages, but appeared and rapidly increased only at the stage of weaning. Exon 2 transcripts in kidney also did not appear until the postnatal period. These data suggest tissue-specific and developmentally regulated transcription factors regulating IGF-I promoter activity or, alternatively, tissue-specific and developmental stage-dependent differences in the stability of IGF-I mRNAs resulting from the use of different transcription start sites. These different mRNAs may be of significance in the differential regulation of IGF-I production for autocrine or paracrine function.
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DOI：
10.1016/s0021-9258(18)92881-4
发表时间：
1991-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Y. Kajimoto;P. Rotwein
通讯作者：
Y. Kajimoto;P. Rotwein
胰岛素样生长因子的马赛克进化。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shimatsu,A;Rotwein,P
通讯作者：
Rotwein,P
大鼠胎儿和成人组织中的生长调节素-C/胰岛素样生长因子-I 和胰岛素样生长因子-II mRNA。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lund,PK;Moats-Staats,BM;Hynes,MA;Simmons,JG;Jansen,M;D'Ercole,AJ;VanWyk,JJ
通讯作者：
VanWyk,JJ
两种大鼠胰岛素样生长因子 I mRNA 的序列在 5 非翻译区有所不同。
影响因子：
14.9
作者：
Shimatsu,A;Rotwein,P
通讯作者：
Rotwein,P