Dynamics of enhancers in myeloid antigen presenting cells upon LPS stimulation

BMC Genomics

Research

Yutaka Suzuki¹  Osamu Takeuchi²  Daron M Standley³  Alexis Vandenbon⁴  Shunsuke Teraguchi⁵ 

[1] Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8568, Kashiwa, Japan;Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, 606-8507, Kyoto, Japan;Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, 565-0871, Suita, Japan;Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, 565-0871, Suita, Japan;Immuno-Genomics Research Unit, Immunology Frontier Research Center, Osaka University, 565-0871, Suita, Japan;Quantitative Immunology Research Unit, Immunology Frontier Research Center, Osaka University, 565-0871, Suita, Japan;

关键词: Enhancer Region;    Repressive Marker H3K27me3;    Locate Enhancer;    Early Induction Gene;    ATF3 Binding;   

DOI  :  10.1186/1471-2164-15-S10-S4

来源: Springer

【 摘 要 】

BackgroundRecent studies have underscored the role of enhancers in defining cell type-specific transcriptomes. Cell type-specific enhancers are bound by combinations of shared and cell type-specific transcription factors (TFs). However, little is known about combinatorial binding of TFs to enhancers, dynamics of TF binding following stimulation, or the downstream effects on gene expression. Here, we address these questions in two types of myeloid antigen presenting cells (APCs), macrophages and dendritic cells (DCs), before and after stimulation with lipopolysaccharide (LPS), a potent stimulator of the innate immune response.ResultsWe classified enhancers according to the combination of TFs binding them. There were significant correlations between the sets of TFs bound to enhancers prior to stimulation and expression changes of nearby genes after stimulation. Importantly, a set of enhancers pre-bound by PU.1, C/EBPβ, ATF3, IRF4, and JunB was strongly associated with induced genes and binding by stimulus-activated regulators. Our classification suggests that transient loss of ATF3 binding to a subset of these enhancers is important for regulation of early-induced genes. Changes in TF-enhancer binding after stimulation were correlated with binding by additional activated TFs and with the presence of proximally located enhancers.ConclusionsThe results presented in this study reveal the complexity and dynamics of TF- enhancer binding before and after stimulation in myeloid APCs.

【 授权许可】

CC BY   
© Vandenbon et al.; licensee BioMed Central Ltd. 2014