Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro
Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro
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DOI：
10.1073/pnas.94.6.2261
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发表时间：
1997-03-18
影响因子：
11.1
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
Meisterernst, M;Stelzer, G;Roeder, RG
哺乳动物细胞含有放大激活剂对体外II类基因转录的作用的活性，这些辅因子活性中的几种的分子身份仍然是未知的。在这里，我们确定聚（ADP-核糖）聚合酶（PARP）作为一个功能组件的积极辅因子1的活动。PARP通过在起始前复合物形成过程中起作用来增强转录，但在转录因子IID结合后的一个步骤。这种转录激活需要氨基末端DNA结合结构域，但不需要羧基末端催化区。在纯化的系统中，共激活因子功能需要PARP的摩尔数超过模板的数量，如对于其他DNA结合辅因子如拓扑异构酶I所报道的，PARP对超螺旋模板的作用是DNA浓度依赖性的，并且不依赖于受损的DNA，PARP共激活因子功能被NAD（+）抑制，可能是自身ADP核糖基化的结果。这些观察结果提供了另一个例子，增强转录的某些DNA结合辅因子，并可能指向PARP与RNA聚合酶II相关因子在特殊情况下的相互作用。
Mammalian cells contain activities that amplify the effects of activators on class II gene transcription in vitro, The molecular identity of several of these cofactor activities is still unknown. Here we identify poly(ADP-ribose) polymerase (PARP) as one functional component of the positive cofactor 1 activity. PARP enhances transcription by acting during preinitiation complex formation, but at a step after binding of transcription factor IID. This transcriptional activation requires the amino-terminal DNA-binding domain, but not the carboxyl-terminal catalytic region. In purified systems, coactivator function requires a large molar excess of PARP over the number of templates, as reported for other DNA-binding cofactors such as topoisomerase I, PARP effects on supercoiled templates are DNA concentration-dependent and do not depend on damaged DNA, The PARP coactivator function is suppressed by NAD(+), probably as a result of auto-ADP-ribosylation. These observations provide another example of the potentiation of trancription by certain DNA-binding cofactors and may point to interactions of PARP with RNA polymerase II-associated factors in special situations.