Park Young-Jun, Chodaparambil Jayanth V, Bao Yunhe, McBryant Steven J, Luger Karolin
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA.
J Biol Chem. 2005 Jan 21;280(3):1817-25. doi: 10.1074/jbc.M411347200. Epub 2004 Oct 30.
Eukaryotic chromatin is highly dynamic and turns over rapidly even in the absence of DNA replication. Here we show that the acidic histone chaperone nucleosome assembly protein 1 (NAP-1) from yeast reversibly removes and replaces histone protein dimer H2A-H2B or histone variant dimers from assembled nucleosomes, resulting in active histone exchange. Transient removal of H2A-H2B dimers facilitates nucleosome sliding along the DNA to a thermodynamically favorable position. Histone exchange as well as nucleosome sliding is independent of ATP and relies on the presence of the C-terminal acidic domain of yeast NAP-1, even though this region is not required for histone binding and chromatin assembly. Our results suggest a novel role for NAP-1 (and perhaps other acidic histone chaperones) in mediating chromatin fluidity by incorporating histone variants and assisting nucleosome sliding. NAP-1 may function either untargeted (if acting alone) or may be targeted to specific regions within the genome through interactions with additional factors.
真核染色质具有高度动态性，即使在没有DNA复制的情况下也会快速周转。我们在此表明，来自酵母的酸性组蛋白伴侣核小体组装蛋白1（NAP-1）可逆地从组装好的核小体中去除并替换组蛋白二聚体H2A-H2B或组蛋白变体二聚体，从而导致活跃的组蛋白交换。H2A-H2B二聚体的短暂去除促进核小体沿着DNA滑动到热力学上有利的位置。组蛋白交换以及核小体滑动不依赖于ATP，并且依赖于酵母NAP-1的C末端酸性结构域的存在，尽管该区域对于组蛋白结合和染色质组装并非必需。我们的结果表明，NAP-1（可能还有其他酸性组蛋白伴侣）在通过掺入组蛋白变体和协助核小体滑动来介导染色质流动性方面具有新作用。NAP-1可能无靶向地发挥作用（如果单独起作用），或者可能通过与其他因子的相互作用靶向基因组内的特定区域。
