Raisner Ryan M, Hartley Paul D, Meneghini Marc D, Bao Marie Z, Liu Chih Long, Schreiber Stuart L, Rando Oliver J, Madhani Hiten D
Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, California 94143, USA.
Cell. 2005 Oct 21;123(2):233-48. doi: 10.1016/j.cell.2005.10.002.
In S. cerevisiae, histone variant H2A.Z is deposited in euchromatin at the flanks of silent heterochromatin to prevent its ectopic spread. We show that H2A.Z nucleosomes are found at promoter regions of nearly all genes in euchromatin. They generally occur as two positioned nucleosomes that flank a nucleosome-free region (NFR) that contains the transcription start site. Astonishingly, enrichment at 5' ends is observed not only at actively transcribed genes but also at inactive loci. Mutagenesis of a typical promoter revealed a 22 bp segment of DNA sufficient to program formation of a NFR flanked by two H2A.Z nucleosomes. This segment contains a binding site of the Myb-related protein Reb1 and an adjacent dT:dA tract. Efficient deposition of H2A.Z is further promoted by a specific pattern of histone H3 and H4 tail acetylation and the bromodomain protein Bdf1, a component of the Swr1 remodeling complex that deposits H2A.Z.
在酿酒酵母中,组蛋白变体H2A.Z沉积在常染色质中沉默异染色质的侧翼,以防止其异位扩散。我们发现,H2A.Z核小体存在于常染色质中几乎所有基因的启动子区域。它们通常以两个定位核小体的形式出现,位于包含转录起始位点的无核小体区域(NFR)两侧。令人惊讶的是,不仅在活跃转录的基因中,而且在非活性位点的5'端也观察到富集。对一个典型启动子的诱变揭示了一段22 bp的DNA片段,足以编程形成一个由两个H2A.Z核小体侧翼的NFR。该片段包含Myb相关蛋白Reb1的结合位点和相邻的dT:dA序列。组蛋白H3和H4尾部乙酰化的特定模式以及溴结构域蛋白Bdf1(一种沉积H2A.Z的Swr1重塑复合物的成分)进一步促进了H2A.Z的有效沉积。