Brand A H, Micklem G, Nasmyth K
MRC Laboratory of Molecular Biology, Cambridge, England.
Cell. 1987 Dec 4;51(5):709-19. doi: 10.1016/0092-8674(87)90094-8.
Repression of the yeast silent mating type loci requires cis-acting sequences located over 1 kb from the regulated promoters. One of these sites, a "silencer," exhibits enhancer-like distance- and orientation-independence. The silencer demonstrates both autonomous replication sequence (ARS) activity and a centromere-like segregation function, suggesting roles for DNA replication and segregation in transcriptional repression. Here we identify three sequences (A, E, and B) involved both in repression and in either ARS or segregation activity. The sequences are functionally redundant: no one is essential for complete transcriptional control, but mutations in any two inactivate the silencer. Surprisingly, elements E and B can each activate transcription from heterologous promoters, and E shows striking homology to several yeast upstream activation sequences. Therefore, sequences individually involved in replication, segregation, and transcriptional activation can, at the silencer, efficiently repress transcription.
酵母沉默交配型基因座的抑制需要位于距调控启动子1 kb以上的顺式作用序列。其中一个位点,即“沉默子”,表现出类似增强子的距离和方向独立性。该沉默子兼具自主复制序列(ARS)活性和着丝粒样分离功能,提示DNA复制和分离在转录抑制中发挥作用。在此,我们鉴定出三个既参与抑制又参与ARS或分离活性的序列(A、E和B)。这些序列在功能上是冗余的:没有一个对于完全的转录控制是必不可少的,但任意两个的突变都会使沉默子失活。令人惊讶的是,元件E和B各自都能激活异源启动子的转录,并且E与几个酵母上游激活序列具有显著的同源性。因此,分别参与复制、分离和转录激活的序列在沉默子处能够有效地抑制转录。