Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14075-80. doi: 10.1073/pnas.1008850107. Epub 2010 Jul 22.
The histone variant H3.3 is implicated in the formation and maintenance of specialized chromatin structure in metazoan cells. H3.3-containing nucleosomes are assembled in a replication-independent manner by means of dedicated chaperone proteins. We previously identified the death domain associated protein (Daxx) and the alpha-thalassemia X-linked mental retardation protein (ATRX) as H3.3-associated proteins. Here, we report that the highly conserved N terminus of Daxx interacts directly with variant-specific residues in the H3.3 core. Recombinant Daxx assembles H3.3/H4 tetramers on DNA templates, and the ATRX-Daxx complex catalyzes the deposition and remodeling of H3.3-containing nucleosomes. We find that the ATRX-Daxx complex is bound to telomeric chromatin, and that both components of this complex are required for H3.3 deposition at telomeres in murine embryonic stem cells (ESCs). These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex.
组蛋白变体 H3.3 参与真核细胞中特化染色质结构的形成和维持。H3.3 包含的核小体通过专门的伴侣蛋白以复制独立的方式组装。我们之前鉴定出死亡域相关蛋白（Daxx）和α-地中海贫血 X 连锁智力迟钝蛋白（ATRX）是 H3.3 相关蛋白。在这里，我们报告说 Daxx 的高度保守的 N 端与 H3.3 核心中的变体特异性残基直接相互作用。重组 Daxx 在 DNA 模板上组装 H3.3/H4 四聚体，并且 ATRX-Daxx 复合物催化 H3.3 包含的核小体的沉积和重塑。我们发现 ATRX-Daxx 复合物与端粒染色质结合，并且该复合物的两个成分都需要在小鼠胚胎干细胞（ESCs）中端粒处沉积 H3.3。这些数据表明 Daxx 作为 H3.3 特异性伴侣蛋白发挥作用，并在 ATRX-Daxx 复合物的背景下促进 H3.3 在异染色质基因座上的沉积。
