An Inexplicable Obscurity Involved With Cisplatin Uncovered

79%) (Giresi et?al., 2007), basal p300 (0.37%) (Ghisletti et?al., 2010), RNA Cisplatin Pol II (0.6%), and noncoding chromatin-associated transcripts (Bhatt et?al., 2012) (Figures S1A and S1B). Although we cannot rule out the existence of additional, as yet unknown features that may be associated with latent enhancers prior to stimulation, these data support the definition of latent enhancers as a class of regulatory elements that cannot be identified in unstimulated cells using currently available markers and appear in terminally differentiated cells conditionally to stimulation. To evaluate the contribution of latent enhancers to the LPS-induced gene expression program, we generated ChIP-seq data sets for RNA Pol II in naive and LPS-stimulated macrophages and analyzed the genomic distribution of latent enhancers relative to the transcription start site (TSS) of LPS-regulated genes. We assigned enhancers from different classes to the nearest gene induced in response to stimulation (Table S2). Proximity to LPS-responsive genes was different among enhancer classes, latent enhancers being generally associated with LPS-inducible genes (p?find protocol enhancers (p?= 1.5?�� 10?8 and p?= 2.8?�� 10?25) (Figure?S1C). We then scored latent enhancers for the associated functional categories of the nearby genes using an independent approach (McLean et?al., 2010). Strong functional enrichments were observed (Figure?1E), suggesting that latent enhancers contribute to the activation of specific components of the LPS response. Genes find more are activated by LPS with very different kinetics. Therefore, we analyzed the association of latent enhancers with genes activated at different times after LPS stimulation. Considering the seven recently reported kinetic classes of LPS-induced genes (Bhatt et?al., 2012), we found that the classes of genes with faster activation kinetics were underrepresented among the inducible genes associated with latent enhancers (p?= 8.9?�� 10?6 in a chi-squared test). Therefore, latent enhancers may be mainly dedicated to the activation of slowly induced genes. Conversely, no obvious bias was observed for genes subjected or not to LPS tolerance (i.e., genes resistant to a second LPS stimulation) (Foster et?al., 2007). Additional features that support the functionality of latent enhancers include: (1) their sequence conservation (Figure?S1D),?(2) the enrichment for specific TFBS (Table S3), and (3) their ability to promote expression of a reporter gene driven?by?a minimal promoter (14/24, 58.8% of tested enhancers)?(Figure?S1E).