2 response genes, secondary response genes need new protein synthesis to establish full expression patterns. This complex regulation depends on an array of transcription factors that may be divided in four classes (Table 1 ). The first two classes of transcription factors are ubiquitous stress sensors that respond to external stress signals. Class I includes constitutively expressed transcription factors, such as NF-κB and IRF3, activated by signaldependent post-translational modifications that

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... affect their activation properties and nuclear localization. For example, cytoplasmic NF-κB is rapidly translocated to the nucleus after LPS stimulation, and is involved in the induction of primary genes. Other transcription factors of this class include latent nuclear AP-1 transcription factors, such as c-Jun phosphorylated rapidly after LPS stimulation. Class II transcription factors, including C/EBP and AP-1 transcription factor family members, need new protein synthesis for LPSdependent stimulation. In addition to inducing secondary late gene expression, these transcription factors play a role in determining waves of time-dependent levels of gene expression. In macrophages, CCAAT/enhancer-binding protein (C/EBP ) expression is increased late after LPS induction (see below). The two last classes comprise tissue-restricted and cell-lineage transcription factors. The third category includes the macrophage-differentiation transcription factors PU.1 and C/EBP . Transcription factors of this class establish inducible cell-specific responses to stress and inflammation, by generating macrophage-specific chromatin domain modifications. The fourth category includes metabolic sensors of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXR), activated respectively by fatty acids and cholesterol metabolites (Glass and Saijo, 2010). These ligand-dependent transcription factors are anti-inflammatory and link metabolism and tissue inflammation. Recent findings have uncovered a general view of the various regulatory mechanisms establishing differential gene-specific patterns of primary and secondary gene expression after LPS stimulation in macrophages. These studies have determined the role of transcription factors, chromatin modifications and structure in gene regulation from transcription start sites and proximal promoter elements, or from enhancers, with microarray data generating genome-wide expression patterns, global chromatin immunoprecipitation experiments (ChIPon-ChIP), real-time PCR analysis and massively parallel sequencing.