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: Using a ChIP-seq time series dataset, we found that the timing of H3K27ac accumulation at promoters coincided with their transcriptional induction. However, in contrast, the LPS-induced accumulation of several other histone modifications at promoters and enhancers occurred 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 the timing of TF activation and accumulation of 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 role for STAT1/2 in the regulation of these histone modifications. Conclusions: The timing of several 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 these modifications more likely reflect the activation of stimulus-dependent TFs and their interactions with chromatin modifiers.