Effect of mithramycin on chromatin accessibility (ATAC-Seq). Effect of mithramycin on chromatin accessibility (ATAC-Seq)

Mammalian genome encodes approximately 1,700 transcription factors (TFs), 1,300 out of which have sequence specific binding motifs. Transcription in mammalian cells is regulated by the recruitment of TFs to specific cis-regulatory elements. In spite of consistent efforts on the function of individual TF, the question still remains how TFs bind to DNA and form enhancer. Here, we try to solve this problem by investigating the relationship between TF binding pattern and chromatin accessibility (ATAC-Seq). We first systematically acquired ATAC-Seq dataset as well as matched RNA-Seq dataset from different mouse primary tissues. A comprehensive TF binding map was built for each tissue/cell type by genomic approaches. Overall design: We displaced stripe factors with mithramycin in activated B cell and then checked effect on chromatin accessibility.

哺乳动物基因组编码约1700种转录因子（Transcription Factors，TFs），其中1300种带有序列特异性结合基序。哺乳动物细胞内的转录过程通过将转录因子招募至特定顺式调控元件（cis-regulatory elements）得以调控。尽管学界已针对单个转录因子的功能开展了大量持续研究，但转录因子如何结合DNA并形成增强子（enhancer）这一科学问题仍未得到解答。本研究通过探究转录因子结合模式与染色质可及性（ATAC-Seq）之间的关联，旨在解决上述问题。研究团队首先系统地从多种小鼠原代组织中获取了ATAC-Seq数据集与匹配的RNA-Seq数据集，并通过基因组学方法为每种组织/细胞类型构建了全面的转录因子结合图谱。实验设计：本研究在活化B细胞中利用光神霉素阻断条纹因子的功能，随后检测其对染色质可及性的影响。