Gutiérrez José, Paredes Roberto, Cruzat Fernando, Hill David A, van Wijnen Andre J, Lian Jane B, Stein Gary S, Stein Janet L, Imbalzano Anthony N, Montecino Martin
Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Barrio Universitario s/n, Casilla 160-C, Concepcion 4079100, Chile.
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655.
J Biol Chem. 2007 Mar 30;282(13):9445-9457. doi: 10.1074/jbc.M609847200. Epub 2007 Feb 1.
Changes in local chromatin structure accompany transcriptional activation of eukaryotic genes. In vivo these changes in chromatin organization can be catalyzed by ATP-dependent chromatin-remodeling complexes, such as SWI/SNF. These complexes alter the tight wrapping of DNA in the nucleosomes and can facilitate the mobilization of the histone octamer to adjacent DNA segments, leaving promoter regulatory elements exposed for transcription factor binding. To gain understanding of how the activity of SWI/SNF complexes may be modulated by the different DNA sequences within a natural promoter, we have reconstituted nucleosomes containing promoter segments of the transcriptionally active cell type-specific osteocalcin (OC) gene and determined how they affect the directional movements of the nucleosomes. Our results indicate that SWI/SNF complexes induce octamer sliding to preferential positions in the OC promoter, leading to a nucleosomal organization that resembles that described in intact cells expressing the OC gene. Our studies demonstrate that the position of the histone octamer is primarily determined by sequences within the OC promoter that include or exclude nucleosomes. We propose that these sequences are critical components of the regulatory mechanisms that mediate expression of this tissue-specific gene.
局部染色质结构的变化伴随着真核基因的转录激活。在体内,染色质组织的这些变化可由ATP依赖的染色质重塑复合物催化,如SWI/SNF。这些复合物改变核小体中DNA的紧密缠绕,并能促进组蛋白八聚体向相邻DNA片段的移动,使启动子调控元件暴露出来以便转录因子结合。为了了解SWI/SNF复合物的活性如何被天然启动子内的不同DNA序列调节,我们重建了含有转录活性的细胞类型特异性骨钙素(OC)基因启动子片段的核小体,并确定它们如何影响核小体的定向移动。我们的结果表明,SWI/SNF复合物诱导八聚体滑动到OC启动子中的优先位置,导致核小体组织类似于在表达OC基因的完整细胞中所描述的那样。我们的研究表明,组蛋白八聚体的位置主要由OC启动子内包含或排除核小体的序列决定。我们提出,这些序列是介导该组织特异性基因表达的调控机制的关键组成部分。