| 研究概要 |
This year we completed the final ChIP-seq experiments, for H3K27ac and H3K9K14ac, thus completing our large-scale dataset of histone modifications and RNA Polymerase II (RNAP) binding in dendritic cells.
On the computational level, used this dataset to analyze the genome-wide epigenetic changes in dendritic cells following immune stimulation by LPS. First, we integrated the new data with the ChIP-seq data we acquired previously as part of this grant, and with other data we obtained for the same cell type treated with the same stimulus. We developed a method for processing and normalizing such large-scale ChIP-seq time series data, for which we are preparing a paper. We are also constructing a public database for storing and visualization of data and results (http://sysimm.ifrec.osaka-u.ac.jp/genomebrowser/).
Using the processed data, we defined promoter and enhancer regions, and we analyzed the dynamics of histone modifications and RNAP binding in these regions after stimulation, and their influence on gene expression. We particularly focused on LPS-induced de novo appearing enhancer regions, and interactions between changes in histone modifications and TF binding.
Finally, we completed a study of enhancers and promoters in macrophages, using publicly available histone modification data. We found that a small set of TFs is preferentially bound to enhancers that control LPS-induced genes. We also found that stimulation induces considerable dynamics TF binding at enhancers, and that a particular pattern of TF binding changes is associated with early, transient gene induction.
|
