Mitogenic activation of normal T cells leads to increased initiation of transcription in the c-myc locus.
Mitogenic activation of normal T cells leads to increased initiation of transcription in the c-myc locus.
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正常 T 细胞的有丝分裂激活导致 c-myc 基因座转录起始增加。
DOI：
10.1016/s0021-9258(18)68860-x
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Ulrich Siebenlistt
中科院分区：
文献类型：
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作者：
Kathleen Kelly;Ulrich Siebenlistt
在促有丝分裂激活的早期，正常人T细胞表达水平升高的稳态mRNA，其编码核定位的原癌基因c-fos、c-myc和c-myb。虽然负责增加这些特定的mRNA的机制是未知的，最近的证据表明，上调c-myc可能是由于释放一个新生的链延长块。c-myc的连续转录分析表明，在激活的T细胞中，c-myc mRNA水平升高主要是由于起始增加而不是延长效率的调节。c-myc的转录刺激开始于似乎准备激活的染色质状态。如通过DNase I超敏位点分析所确定的，静息T细胞中c-myc的染色质结构类似于表达高水平c-myc的其他细胞类型的染色质结构，此外，超敏位点的变化与c-myc转录的促有丝分裂刺激无关。由于有丝分裂原诱导的上调和终末分化相关的下调c-myc的机制不同，似乎c-myc受到各种不同的转录控制。除了c-myc之外，c-fos和c-myb也显示出在T细胞中通过转录机制诱导。
Early following mitogenic activation, normal human T cells express elevated levels of steady-state mRNAs encoding the nuclear-localized protooncogenes, c-fos, c-myc, and c-myb. Although the mechanisms responsible for increases in these specific mRNAs are not known, recent evidence suggests that up-regulation of c-myc could result from the release of a nascent chain elongation block. Run-on transcription analyses of c-myc show here that increased initiation and not modulation of elongation efficiency is largely responsible for elevated c-myc mRNA levels in activated T cells. Transcriptional stimulation of c-myc commences from a chromatin state that appears poised for activation. As determined by DNase I hypersensitive site analyses, the chromatin structure of c-myc in resting T cells resembles that of other cell types expressing high levels of c-myc, and furthermore, no changes in hypersensitive sites can be correlated with mitogenic stimulation of c-myc transcription. Because mitogen-induced up-regulation and terminal differentiation-associated down-regulation of c-myc are mechanistically different, it appears that c-myc is subject to a variety of distinct transcriptional controls. In addition to c-myc, c-fos and c-myb are shown to be induced via a transcriptional mechanism in T cells.