Walfridsson Julian, Khorosjutina Olga, Matikainen Paulina, Gustafsson Claes M, Ekwall Karl
Karolinska Institutet, Department of Biosciences and Medical Nutrition/School of Life Sciences, University College Sodertorn, Alfred Nobel's Allé 7, 141 89 Huddinge, Sweden.
EMBO J. 2007 Jun 20;26(12):2868-79. doi: 10.1038/sj.emboj.7601728. Epub 2007 May 17.
Chromatin remodelling factors and histone chaperones were previously shown to cooperatively affect nucleosome assembly and disassembly processes in vitro. Here, we show that Schizosaccharomyces pombe CHD remodellers, the Hrp1 and Hrp3 paralogs physically interact with the histone chaperone Nap1. Genome-wide analysis of Hrp1, Hrp3 and Nap1 occupancy, combined with nucleosome density measurements revealed that the CHD factors and Nap1 colocalized in particular to promoter regions where they remove nucleosomes near the transcriptional start site. Hrp1 and Hrp3 also regulate nucleosome density in coding regions, where they have redundant roles to stimulate transcription. Previously, DNA replication-dependent and -independent nucleosome disassembly processes have been described. We found that nucleosome density increased in the hrp1 mutant in the absence of DNA replication. Finally, regions where nucleosome density increased in hrp1, hrp3 and nap1 mutants also showed nucleosome density and histone modification changes in HDAC and HAT mutants. Thus, this study revealed an important in vivo role for CHD remodellers and Nap1 in nucleosome disassembly at promoters and coding regions, which are linked to changes in histone acetylation.
染色质重塑因子和组蛋白伴侣先前已被证明在体外协同影响核小体的组装和拆卸过程。在此，我们表明粟酒裂殖酵母CHD重塑因子Hrp1和Hrp3旁系同源物与组蛋白伴侣Nap1发生物理相互作用。对Hrp1、Hrp3和Nap1占据情况进行全基因组分析，并结合核小体密度测量结果显示，CHD因子和Nap1特别共定位于启动子区域，在那里它们去除转录起始位点附近的核小体。Hrp1和Hrp3还调节编码区域的核小体密度，在这些区域它们具有刺激转录的冗余作用。此前，已描述了依赖DNA复制和不依赖DNA复制的核小体拆卸过程。我们发现，在没有DNA复制的情况下，hrp1突变体中的核小体密度增加。最后，在hrp1、hrp3和nap1突变体中核小体密度增加的区域，在HDAC和HAT突变体中也显示出核小体密度和组蛋白修饰的变化。因此，本研究揭示了CHD重塑因子和Nap1在启动子和编码区域的核小体拆卸中在体内的重要作用，这与组蛋白乙酰化的变化有关。
