Cutting the chain of command: specific inhibitors of transcription.
Cutting the chain of command: specific inhibitors of transcription.
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切断指挥链：特异性转录抑制剂。
DOI：
10.1089/ard.1991.1.365
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Holt,JT
中科院分区：
文献类型：
--
作者：
Holt,JT
细胞生长和分化（至少部分）受基因转录变化的调节。转录因子的克隆和表征揭示了这些因子协调调节特定遗传程序的转录;例如，通过转录因子Fos和Jun与特定DNA序列的结合来激活许多佛波酯诱导的基因。显然，抑制特定转录因子的产生或功能，将改变整个遗传程序，改变大量基因的表达（类似于切断军事指挥链，影响整个旅或师）。我们的实验室和其他实验室已经采用遗传学方法，通过两种不同的方法特异性抑制转录：（1）反义抑制转录因子的产生;（2）引入靶DNA序列以“吸收“或淬灭转录因子。在这份报告中，我们目前的数据表明，血清刺激诱导的c-fosgene可能会减少90%以上的引入含有血清反应元件（SRE）的靶DNA序列;相同数量的突变SRE序列对基因诱导没有影响。这些研究表明，特异性转录抑制剂可以对细胞基因表达产生显著影响。挑战在于调节转录程序而不对正常细胞产生有害影响。
Cell growth and differentiation are regulated (at least in part) by changes in gene transcription. The cloning and characterization of transcription factors has revealed that these factors coordinately regulate the transcription of specific genetic programs; for example, a number of phorbol ester-induced genes are activated by binding of the transcription factors Fos and Jun to specific DNA sequences. Clearly, inhibition of either the production or function of specific transcription factors would alter complete genetic programs, changing the expression of a great number of genes (analogous to cutting the chain of military command and affecting an entire brigade or division). Our laboratory and others have employed genetic methods to specifically inhibit transcription by two distinct methods: (1) antisense inhibition of the production of transcription factors; and (2) introduction of target DNA sequences to "soak up"or quench transcription factors. In this report, we present data showing that serum-stimulated induction of the c-fosgene may be reduced more than 90% by introduction of target DNA sequences containing the serum response element (SRE); identical amounts of mutant SRE sequences have no effect on gene induction. These studies demonstrate that specific inhibitors of transcription can have significant effects on cellular gene expression. The challenge is to modulate transcriptional programs without deleterious effects on normal cells.