Williams Stephanie K, Truong David, Tyler Jessica K
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9000-5. doi: 10.1073/pnas.0800057105. Epub 2008 Jun 24.
Promoter chromatin disassembly is a widely used mechanism to regulate eukaryotic transcriptional induction. Delaying histone H3/H4 removal from the yeast PHO5 promoter also leads to delayed removal of histones H2A/H2B, suggesting a constant equilibrium of assembly and disassembly of H2A/H2B, whereas H3/H4 disassembly is the highly regulated step. Toward understanding how H3/H4 disassembly is regulated, we observe a drastic increase in the levels of histone H3 acetylated on lysine-56 (K56ac) during promoter chromatin disassembly. Indeed, promoter chromatin disassembly is driven by Rtt109 and Asf1-dependent acetylation of H3 K56. Conversely, promoter chromatin reassembly during transcriptional repression is accompanied by decreased levels of histone H3 acetylated on lysine-56, and a mutation that prevents K56 acetylation increases the rate of transcriptional repression. As such, H3 K56 acetylation drives chromatin toward the disassembled state during transcriptional activation, whereas loss of H3 K56 acetylation drives the chromatin toward the assembled state.
启动子染色质解聚是一种广泛用于调控真核生物转录诱导的机制。延迟从酵母PHO5启动子上移除组蛋白H3/H4也会导致组蛋白H2A/H2B的移除延迟,这表明H2A/H2B的组装和解聚存在持续的平衡,而H3/H4的解聚是高度受调控的步骤。为了理解H3/H4解聚是如何被调控的,我们观察到在启动子染色质解聚过程中,赖氨酸56(K56ac)乙酰化的组蛋白H3水平急剧增加。事实上,启动子染色质解聚是由Rtt109和Asf1依赖的H3 K56乙酰化驱动的。相反,转录抑制过程中的启动子染色质重新组装伴随着赖氨酸56乙酰化的组蛋白H3水平降低,并且阻止K56乙酰化的突变会增加转录抑制的速率。因此,H3 K56乙酰化在转录激活过程中驱使染色质趋向解聚状态,而H3 K56乙酰化的缺失则驱使染色质趋向组装状态。