GAGA can mediate enhancer function in trans by linking two separate DNA molecules
GAGA can mediate enhancer function in trans by linking two separate DNA molecules
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DOI：
10.1093/emboj/21.7.1775
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发表时间：
2002-04-02
期刊：
影响因子：
11.4
通讯作者：
Verrijzer, CP
中科院分区：
文献类型：
--
作者：
Mahmoudi, T;Katsani, KR;Verrijzer, CP
增强子被定义为顺式作用DNA序列，其以与距离和方向无关的方式刺激连接的启动子的转录。增强子如何在后生动物基因组内跨遥远的染色体距离激活基因转录仍然知之甚少。在这里，我们证明转录因子 GAGA 可以通过将增强子与其同源启动子连接来刺激转录。引人注目的是，除了促进顺式远程增强子的激活之外，GAGA 还可以通过位于单独 DNA 分子上的增强子指导启动子的激活。反式增强子功能主要依赖于 POZ 结构域介导的 GAGA 寡聚化，使 GAGA 能够同时结合两个 DNA 分子。在转染细胞和重建的转录反应中均观察到由在性状中起作用的增强子引起的转录激活。我们认为 GAGA 通过提供介导增强子-启动子通讯的蛋白质桥来促进长程激活。
Enhancers have been defined as cis-acting DNA sequences that stimulate transcription from a linked promoter in a distance- and orientation-independent manner. How enhancers activate gene transcription over vast chromosomal distances within metazoan genomes remains poorly understood. Here, we show that the transcription factor GAGA can stimulate transcription by linking an enhancer to its cognate promoter. Strikingly, in addition to facilitating activation by a remote enhancer in cis, GAGA can direct activation of a promoter by an enhancer located on a separate DNA molecule. Enhancer function in trans is critically dependent on POZ domain-mediated GAGA oligomerization, enabling GAGA to bind two DNA molecules simultaneously. Transcriptional activation by an enhancer functioning in traits was observed both in transfected cells and in reconstituted transcription reactions. We propose that GAGA facilitates long-range activation by providing a protein bridge that mediates enhancer-promoter communication.