TY - JOUR T1 - Waves of chromatin modifications in mouse dendritic cells in response to LPS stimulation JF - bioRxiv DO - 10.1101/066472 SP - 066472 AU - Alexis Vandenbon AU - Yutaro Kumagai AU - Mengjie Lin AU - Yutaka Suzuki AU - Kenta Nakai Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/28/066472.abstract N2 - Background The importance of transcription factors (TFs) and epigenetic modifications in the control of gene expression is widely accepted. However, causal relationships between changes in TF binding, histone modifications, and gene expression during the response to extracellular stimuli are not well understood. Here, we analyzed the ordering of these events on a genome-wide scale in dendritic cells (DCs) in response to lipopolysaccharide (LPS) stimulation.Results We found that LPS-induced increases in several histone modifications at promoters and enhancers occur in “waves” within specific time frames after stimulation, independent of the timing of transcriptional induction. Integrative analysis with TF binding data revealed potential links between TF binding and histone modifications. Especially, binding by STAT1/2 coincided with induction of H3K9K14ac, and was followed by increases in H3K4me3. In a subset of LPS-induced genes the induction of these modifications was found to be TRIF-, IRF3-, and IFNR-dependent, further supporting a possible role for STAT1/2 in the regulation of these histone modifications.Conclusions The timing of stimulus-induced, short-term changes in histone modifications appears to be relatively independent of dynamics in activity of regulatory regions. This suggests a lack of a direct causal relationship. Changes in modifications more likely reflect the activation of stimulus-dependent TFs and their interactions with chromatin modifiers. ER -