McPherson C E, Shim E Y, Friedman D S, Zaret K S
Section of Biochemistry, Brown University, Providence, Rhode Island 02912.
Cell. 1993 Oct 22;75(2):387-98. doi: 10.1016/0092-8674(93)80079-t.
Nucleosomes positioned over promoters are usually inhibitory to protein binding and activity. We analyzed at the nucleotide level of resolution the nucleosomal organization of a distal, liver-specific enhancer in various mouse tissues and found that the enhancer exists in an array of three precisely positioned nucleosomes only in liver chromatin, where the enhancer is active. In vivo footprinting reveals that essential transcription factor-binding sites are occupied on apparent nucleosome surfaces, in one case leading to a perturbed nucleosomal structure. A similar nucleosomal array is generated with an in vitro chromatin assembly system in which nucleosome positioning is dependent upon binding to the enhancer of proteins related to hepatocyte nuclear factor 3. We suggest that certain transcription factors can organize nucleosomal structures that define an active enhancer element.
位于启动子上的核小体通常会抑制蛋白质结合及活性。我们在核苷酸分辨率水平上分析了不同小鼠组织中一个远端肝脏特异性增强子的核小体组织情况，发现该增强子仅在肝脏染色质中以三个精确定位的核小体阵列形式存在，而在肝脏中该增强子具有活性。体内足迹法显示，关键转录因子结合位点位于明显的核小体表面，在一种情况下会导致核小体结构受到干扰。利用体外染色质组装系统也能产生类似的核小体阵列，其中核小体定位取决于与肝细胞核因子3相关的蛋白质与增强子的结合。我们认为某些转录因子可以组织核小体结构，从而定义一个活性增强子元件。
