Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción 4070043, Chile.
Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA.
Biochim Biophys Acta Gene Regul Mech. 2017 Mar;1860(3):316-326. doi: 10.1016/j.bbagrm.2017.01.002. Epub 2017 Jan 9.
Diverse chromatin modifiers are involved in regulation of gene expression at the level of transcriptional regulation. Among these modifiers are ATP-dependent chromatin remodelers, where the SWI/SNF complex is the founding member. It has been observed that High Mobility Group (HMG) proteins can influence the activity of a number of these chromatin remodelers. In this context, we have previously demonstrated that the yeast HMG proteins Nhp6 and Hmo1 can stimulate SWI/SNF activity. Here, we studied the genome-wide binding patterns of Nhp6, Hmo1 and the SWI/SNF complex, finding that most of gene promoters presenting high occupancy of this complex also display high enrichment of these HMG proteins. Using deletion mutant strains we demonstrate that binding of SWI/SNF is significantly reduced at numerous genomic locations by deletion of NHP6 and/or deletion of HMO1. Moreover, alterations in the nucleosome landscape take place at gene promoters undergoing reduced SWI/SNF binding. Additional analyses show that these effects also correlate with alterations in transcriptional activity. Our results suggest that, besides the ability to stimulate SWI/SNF activity, these HMG proteins are able to assist the loading of this complex onto gene regulatory regions.
多种染色质修饰物参与转录调控水平的基因表达调控。这些修饰物包括 ATP 依赖性染色质重塑剂，其中 SWI/SNF 复合物是创始成员。已经观察到高迁移率族（HMG）蛋白可以影响许多这些染色质重塑剂的活性。在这方面，我们之前已经证明酵母 HMG 蛋白 Nhp6 和 Hmo1 可以刺激 SWI/SNF 活性。在这里，我们研究了 Nhp6、Hmo1 和 SWI/SNF 复合物的全基因组结合模式，发现大多数呈现该复合物高占有率的基因启动子也显示出这些 HMG 蛋白的高富集。使用缺失突变株，我们证明通过缺失 NHP6 和/或缺失 HMO1，SWI/SNF 在许多基因组位置的结合显著减少。此外，在经历 SWI/SNF 结合减少的基因启动子处发生核小体景观的改变。进一步的分析表明，这些效应也与转录活性的改变相关。我们的结果表明，除了刺激 SWI/SNF 活性的能力外，这些 HMG 蛋白还能够帮助该复合物加载到基因调控区域。
