Banerjee Sharmi, Zhu Hongxiao, Tang Man, Feng Wu-Chun, Wu Xiaowei, Xie Hehuang
Bradley Department of Electrical and Computer Engineering, Virginia Tech, Blacksburg, VA, United States.
Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States.
Front Genet. 2019 Jan 15;9:731. doi: 10.3389/fgene.2018.00731. eCollection 2018.
Gene expression regulation is a complex process involving the interplay between transcription factors and chromatin states. Significant progress has been made toward understanding the impact of chromatin states on gene expression. Nevertheless, the mechanism of transcription factors binding combinatorially in different chromatin states to enable selective regulation of gene expression remains an interesting research area. We introduce a nonparametric Bayesian clustering method for inhomogeneous Poisson processes to detect heterogeneous binding patterns of multiple proteins including transcription factors to form regulatory modules in different chromatin states. We applied this approach on ChIP-seq data for mouse neural stem cells containing 21 proteins and observed different groups or modules of proteins clustered within different chromatin states. These chromatin-state-specific regulatory modules were found to have significant influence on gene expression. We also observed different motif preferences for certain TFs between different chromatin states. Our results reveal a degree of interdependency between chromatin states and combinatorial binding of proteins in the complex transcriptional regulatory process. The software package is available on Github at - https://github.com/BSharmi/DPM-LGCP.
基因表达调控是一个复杂的过程，涉及转录因子与染色质状态之间的相互作用。在理解染色质状态对基因表达的影响方面已经取得了重大进展。然而，转录因子在不同染色质状态下组合结合以实现基因表达的选择性调控的机制仍然是一个有趣的研究领域。我们引入了一种用于非齐次泊松过程的非参数贝叶斯聚类方法，以检测包括转录因子在内的多种蛋白质的异质结合模式，从而在不同染色质状态下形成调控模块。我们将这种方法应用于包含21种蛋白质的小鼠神经干细胞的ChIP-seq数据，并观察到不同的蛋白质组或模块聚集在不同的染色质状态中。发现这些特定于染色质状态的调控模块对基因表达有显著影响。我们还观察到不同染色质状态下某些转录因子的基序偏好不同。我们的结果揭示了在复杂的转录调控过程中染色质状态与蛋白质组合结合之间的一定程度的相互依赖性。该软件包可在Github上获取，网址为 - https://github.com/BSharmi/DPM-LGCP。
