Chromatin state and microRNA determine different gene expression dynamics responsive to TNF stimulation

Gene expression is a dynamic process, and what factors influence gene expression changes upon external stimulus have not been clearly understood. We studied gene expression profiles in human umbilical vein endothelial cells (HUVEC) after the Tumor Necrosis Factor (TNF) stimulus, and found that: the promoters of fast-response up-regulated genes were enriched with several “active” chromatin markers like H3K27ac and H3K4me3, and also preferentially bound by Pol II and c-Myc; the core-promoter regions of slow-response up-regulated genes were frequently occupied by nucleosomes; down-regulated genes were more intensively regulated by microRNAs. Moreover, the Gene Ontology and motif analysis of the promoter regions revealed that gene clusters with different response behaviors had different functions and were regulated by different sets of transcription factors. Our observations suggested that the different gene expression patterns upon external stimulus were regulated by a combination of multi-layer regulators.

► Gene clusters with different expression patterns induced by TNF were revealed.
► Chromatin states influence the response speeds of induced genes.
► Gene clusters with different response speeds were regulated by different sets of TFs.
► Down-regulated genes were intensively regulated by microRNAs.