染色质重塑因子Chd1在核小体DNA螺旋间的结构域间通讯
Interdomain Communication of the Chd1 Chromatin Remodeler across the DNA Gyres of the Nucleosome.
作者信息
Nodelman Ilana M, Bleichert Franziska, Patel Ashok, Ren Ren, Horvath Kyle C, Berger James M, Bowman Gregory D
机构信息
T.C. Jenkins Department of Biophysics, Johns Hopkins University, 302 Jenkins Hall, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
出版信息
Mol Cell. 2017 Feb 2;65(3):447-459.e6. doi: 10.1016/j.molcel.2016.12.011. Epub 2017 Jan 19.
Chromatin remodelers use a helicase-like ATPase motor to reposition and reorganize nucleosomes along genomic DNA. Yet, how the ATPase motor communicates with other remodeler domains in the context of the nucleosome has so far been elusive. Here, we report for the Chd1 remodeler a unique organization of domains on the nucleosome that reveals direct domain-domain communication. Site-specific cross-linking shows that the chromodomains and ATPase motor bind to adjacent SHL1 and SHL2 sites, respectively, on nucleosomal DNA and pack against the DNA-binding domain on DNA exiting the nucleosome. This domain arrangement spans the two DNA gyres of the nucleosome and bridges both ends of a wrapped, ∼90-bp nucleosomal loop of DNA, suggesting a means for nucleosome assembly. This architecture illustrates how Chd1 senses DNA outside the nucleosome core and provides a basis for nucleosome spacing and directional sliding away from transcription factor barriers.
染色质重塑因子利用一种类似解旋酶的ATP酶马达沿着基因组DNA重新定位和重组核小体。然而，到目前为止，ATP酶马达在核小体环境中如何与其他重塑因子结构域进行通讯仍是未知的。在这里，我们报道了Chd1重塑因子在核小体上独特的结构域组织，揭示了直接的结构域-结构域通讯。位点特异性交联表明，染色质结构域和ATP酶马达分别结合在核小体DNA上相邻的SHL1和SHL2位点，并与从核小体中出来的DNA上的DNA结合结构域紧密排列。这种结构域排列跨越了核小体的两个DNA螺旋，并连接了一个包裹着的约90个碱基对的核小体DNA环的两端，提示了一种核小体组装方式。这种结构说明了Chd1如何感知核小体核心外的DNA，并为核小体间距和远离转录因子屏障的定向滑动提供了基础。
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