Nucleosome occupancy as a novel chromatin parameter for replication origin functions.
Nucleosome occupancy as a novel chromatin parameter for replication origin functions.
复制标题
DOI：
10.1101/gr.209940.116
复制
发表时间：
2017-02
期刊：
影响因子：
7
通讯作者：
Tsukiyama T
中科院分区：
文献类型：
--
作者：
Rodriguez J;Lee L;Lynch B;Tsukiyama T
真核生物的DNA复制始于基因组中的多个离散位置，称为复制起始点。在S阶段之前，多个起源准备通过招募复制前复合体(Pre-RC)来启动复制。为了进行正确的复制，必须严格控制原点激活。在种群水平上，在S期内，每个起源都有不同的激发时间和激活频率。许多研究表明，染色质可以强烈地影响DNA复制的启动。然而，影响来源属性的染色质参数尚未完全确定。我们发现，在整个酿酒酵母基因组中，G1中的核小体占有率在不同的起始点上差异很大，并且起始点周围的核小体占有率与起始点的激活时间和效率以及前RC的形成显著相关。我们进一步证明，在从G2/M到G1的转变过程中，核小体在G1起始点附近的占据是以一种前RC依赖的方式建立的。重要的是，ORC1-161突变体起始点周围核小体占有率的细胞周期变化与全球起始点使用异常相关，这表明适当建立起始点周围核小体占有率是调节全球起始点活动的关键步骤。因此，我们的工作确立了核小体占有率是一个新的和关键的染色质参数，用于适当的起源调控。
Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation.