DNA LOOPING AND SP1 MULTIMER LINKS - A MECHANISM FOR TRANSCRIPTIONAL SYNERGISM AND ENHANCEMENT

被引:222
作者
MASTRANGELO, IA
COUREY, AJ
WALL, JS
JACKSON, SP
HOUGH, PVC
机构
[1] BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973
[2] UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024
[3] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,HOWARD HUGHES MED INST,BERKELEY,CA 94720
关键词
TRANSCRIPTION FACTOR-SP1; ENHANCER MECHANISM; SCANNING TRANSMISSION ELECTRON MICROSCOPY;
D O I
10.1073/pnas.88.13.5670
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Using conventional and scanning transmission electron microscopy, we have examined the physical basis of long-range enhancer effects between distal and proximal elements in a eukaryotic promoter. Specifically, we have studied binding of human transcription factor Sp1 to 10-base-pair G + C-rich elements ("GC boxes") located at -100 and +1700 relative to the RNA start site. It was previously observed that the distantly located site functions in synergism with the promoter-proximal site to strongly activate transcription in vivo. Here we demonstrate that this synergism is likely to be a direct consequence of interactions between remote and local Sp1, the remote Sp1 translocated to the promoter by a DNA loop. Scanning transmission electron microscopy shows that Sp1 initially forms a tetramer and subsequently assembles multiple tetramers stacked in register at the DNA loop juncture. This unexpected finding not only provides the physical basis for loop formation but also defines a biological process leading to strongly increased concentration of activator protein at the promoter. The mechanism may unify the problem of transcriptional activation by removing enhancer action as a separate class of regulatory activity.
引用
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页码:5670 / 5674
页数:5
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