Ramachandran Aruna, Omar Mahera, Cheslock Peter, Schnitzler Gavin R
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
J Biol Chem. 2003 Dec 5;278(49):48590-601. doi: 10.1074/jbc.M309033200. Epub 2003 Sep 25.
Chromatin, a combination of nucleosomes and linker histones, inhibits transcription by blocking polymerase movement and access of factors to DNA. ATP-dependent remodeling complexes such as SWI/SNF and RSC alter chromatin structure to increase or decrease this repression. To further our understanding of how human SWI/SNF (hSWI/SNF) "remodels" chromatin we examined the octamer location, nature, and template specificity of hSWI/SNF-remodeled mononucleosomes when free or bound by linker histone H1. We find that, in the absence of H1, hSWI/SNF consistently moves nucleosomes to DNA ends, regardless of template sequence. On some sequences the repositioned histone octamer appears to be moved approximately 45 bp off the DNA edge, whereas on others it appears to be normal, suggesting that the nature of the remodeled nucleosome can be influenced by DNA sequence. By contrast, in the presence of histone H1, hSWI/SNF slides octamers to more central positions and does not promote nucleosome movement off the ends of the DNA. Our results indicate that the nature and position of hSWI/SNF products may be influenced both by DNA sequence and linker histone, and shed light on the roles of H1 and hSWI/SNF in modulating chromatin structure.
染色质是核小体和连接组蛋白的组合,它通过阻止聚合酶移动以及因子与DNA的结合来抑制转录。依赖ATP的重塑复合物,如SWI/SNF和RSC,会改变染色质结构,以增强或减弱这种抑制作用。为了进一步了解人类SWI/SNF(hSWI/SNF)如何“重塑”染色质,我们研究了游离状态或与连接组蛋白H1结合时,hSWI/SNF重塑的单核小体的八聚体位置、性质和模板特异性。我们发现,在没有H1的情况下,无论模板序列如何,hSWI/SNF都会持续将核小体移至DNA末端。在某些序列上,重新定位的组蛋白八聚体似乎从DNA边缘移开了约45个碱基对,而在其他序列上则似乎正常,这表明重塑的核小体的性质可能受DNA序列影响。相比之下,在存在组蛋白H1的情况下,hSWI/SNF会将八聚体滑向更中心的位置,且不会促进核小体从DNA末端移开。我们的结果表明,hSWI/SNF产物的性质和位置可能受DNA序列和连接组蛋白的影响,并揭示了H1和hSWI/SNF在调节染色质结构中的作用。