Shen Wenlong, Wang Dong, Ye Bingyu, Shi Minglei, Zhang Yan, Zhao Zhihu
Beijing Institute of Biotechnology, No. 20, Dongdajie Street, Beijing, Fengtai District, 100071, China.
College of Life Science, Capital Normal University, 105 Xisihuanbei Road, Beijing, Haidian District, 100048, China.
Biol Res. 2015 May 27;48(1):27. doi: 10.1186/s40659-015-0019-6.
The CCCTC-binding factor (CTCF) is a highly conserved insulator protein that plays various roles in many cellular processes. CTCF is one of the main architecture proteins in higher eukaryotes, and in combination with other architecture proteins and regulators, also shapes the three-dimensional organization of a genome. Experiments show CTCF partially remains associated with chromatin during mitosis. However, the role of CTCF in the maintenance and propagation of genome architectures throughout the cell cycle remains elusive.
We performed a comprehensive bioinformatics analysis on public datasets of Drosophila CTCF (dCTCF). We characterized dCTCF-binding sites according to their occupancy status during the cell cycle, and identified three classes: interphase-mitosis-common (IM), interphase-only (IO) and mitosis-only (MO) sites. Integrated function analysis showed dCTCF-binding sites of different classes might be involved in different biological processes, and IM sites were more conserved and more intensely bound. dCTCF-binding sites of the same class preferentially localized closer to each other, and were highly enriched at chromatin syntenic and topologically associating domains boundaries.
Our results revealed different functions of dCTCF during the cell cycle and suggested that dCTCF might contribute to the establishment of the three-dimensional architecture of the Drosophila genome by maintaining local chromatin compartments throughout the whole cell cycle.
CCCTC结合因子（CTCF）是一种高度保守的绝缘子蛋白，在许多细胞过程中发挥着多种作用。CTCF是高等真核生物中的主要结构蛋白之一，与其他结构蛋白和调节因子一起，也塑造了基因组的三维组织。实验表明，CTCF在有丝分裂期间部分与染色质保持结合。然而，CTCF在整个细胞周期中对基因组结构的维持和传播中的作用仍然不清楚。
我们对果蝇CTCF（dCTCF）的公共数据集进行了全面的生物信息学分析。我们根据其在细胞周期中的占据状态对dCTCF结合位点进行了表征，并确定了三类：间期-有丝分裂共同（IM）、仅间期（IO）和仅有丝分裂（MO）位点。综合功能分析表明，不同类别的dCTCF结合位点可能参与不同的生物学过程，并且IM位点更保守且结合更紧密。同一类别的dCTCF结合位点优先彼此更靠近定位，并且在染色质同线和拓扑相关结构域边界高度富集。
我们的结果揭示了dCTCF在细胞周期中的不同功能，并表明dCTCF可能通过在整个细胞周期中维持局部染色质区室来促进果蝇基因组三维结构的建立。
