LPS, the main component of endotoxins, has been isolated from Gram-negative bacteria and employed to induce microglial activation and initiate several major cellular responses that play important roles in the pathogenesis of inflammation. Thus, the LPS-mediated stimulation of microglia is a Hygromycin B useful model to study the mechanisms underlying neuronal damage mediated through pro-inflammatory and neurotoxic factors, released from activated microglia. To date, several genome-scale studies of LPS-induced BV-2 microglial cells have been conducted to Imidurea determine comprehensive signatures using the microarray method. However, this method has numerous restrictions, such as spatial biases, uneven probe properties, low sensitivity, and dependency on the probes spotted. Next generation sequencing-based technologies, such as RNA-Seq, are increasingly used to study gene expression, as these methods provide unbiased profiles, identify novel transcribed regions compared with microarrays, and can be extremely accurate when a sufficient coverage is obtained. Furthermore, these technologies facilitate the differentiation between the expression of alternative mature mRNAs from the same precursor and the identification of the differential expression of mRNA isoforms. Validation techniques, such as qRT-PCR, have corroborated the accuracy of RNA-Seq; however, a limited number of studies have applied these approaches for the effects of endotoxin infection on changes in global gene expression in macrophages using RNA-Seq analysis. Thus the objective of the present study was to understand host responses to LPS infection in cultured microglial cells using RNA-Seq analysis. In addition to differentially expressed TFs, the annotation of the RNA-Seq data also revealed family-wide DEGs implicated in epigenetic regulation, defined as genetic control through factors other than the DNA sequence. Studies of epigenetic regulation to potentiate innate immune responses have recently emerged.Herein, we provide the first evidence that among multiple families of epigenetic regulators, only histone demethylases and DNA methyltransferase were significantly and differentially expressed in LPS-stimulated BV-2 cells, suggesting that histone demethylases and DNA methyltransferases might be involved in the regulation of BV-2 microglial cell activation.