Côté J, Peterson C L, Workman J L
Laval University Cancer Research Center, Hôtel-Dieu de Québec, Quebec City, Qc G1R 2J6, Canada.
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4947-52. doi: 10.1073/pnas.95.9.4947.
To investigate the mechanism of SWI/SNF action, we have analyzed the pathway by which SWI/SNF stimulates formation of transcription factor-bound nucleosome core complexes. We report here that the SWI/SNF complex binds directly to nucleosome cores and uses the energy of ATP hydrolysis to disrupt histone/DNA interactions, altering the preferred path of DNA bending around the histone octamer. This disruption occurs without dissociating the DNA from the surface of the histone octamer. ATP-dependent disruption of nucleosomal DNA by SWI/SNF generates an altered nucleosome core conformation that can persist for an extended period after detachment of the SWI/SNF complex. This disrupted conformation retains an enhanced affinity for the transcription factor GAL4-AH. Thus, ATP-dependent nucleosome core disruption and enhanced binding of the transcription factor can be temporally separated. These results indicate that SWI/SNF can act transiently in the remodeling of chromatin structure, even before interactions of transcription factors.
为了研究SWI/SNF作用的机制，我们分析了SWI/SNF刺激转录因子结合核小体核心复合物形成的途径。我们在此报告，SWI/SNF复合物直接与核小体核心结合，并利用ATP水解的能量破坏组蛋白/DNA相互作用，改变DNA围绕组蛋白八聚体弯曲的优先路径。这种破坏发生时，DNA并未从组蛋白八聚体表面解离。SWI/SNF对核小体DNA的ATP依赖性破坏产生了一种改变的核小体核心构象，该构象在SWI/SNF复合物脱离后仍能持续较长时间。这种破坏的构象对转录因子GAL4-AH保留了增强的亲和力。因此，ATP依赖性核小体核心破坏和转录因子的增强结合在时间上可以分开。这些结果表明，SWI/SNF甚至在转录因子相互作用之前，就能在染色质结构重塑中短暂发挥作用。
