The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner. Overall design: Lung cancer cell line H23 was treated with JQ1 BET inhibitor. Gene expression profiling by CAGE was performed after 0h, 3h, 6h, 12h and 24h.
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.
Specimen part, Treatment, Subject
View SamplesTranscriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View SamplesTranscriptome analyses of normal gingival fibroblasts after knockdown of DLX5 and RUNX2 long forms.
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View SamplesRNA-seq of normal gingival fibroblasts Overall design: RNA-seq of normal gingival fibroblasts
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part, Subject
View SamplesTo investigate the roles of MYEOV in lung cancer cell proliferation, we compared the expression profiles of A549 lung adenocarcinoma cell lines transfected with control siRNA and siMYEOV.
Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC.
Cell line
View SamplesThe FANTOM5 promoter expression atlas provides a rich source of expression and functional annotation of human and mouse cell-type specific transcriptomes with wide applications in biomedical research.
An atlas of human long non-coding RNAs with accurate 5' ends.
No sample metadata fields
View SamplesCellular replicative senescence, a state of permanent cell-cycle arrest that occurs following an extended period of cell division in culture, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblast cells. We found that both the expression levels of lipid-regulating genes, as well as the abundance of specific lipid families, are actively regulated. We further found that 19 polyunsaturated triacylglycerol species showed the most prominent changes during replicative senescence. We argue that diversion of polyunsaturated fatty acids to glycerolipid biosynthesis could be responsible for the accumulation of specific triacylglycerols. This, in turn, could be one of the cellular mechanisms to prevent lipotoxicity under increased oxidative stress conditions observed during replicative senescence. Collectively, our results place regulation of specific lipid species to a central role during replicative senescence. Overall design: We sequence total RNA from 3 early PD and 3 senesent human BJ cell lines to detect the expressional differences between early PD and senescent cells.
Regulation of lipids is central to replicative senescence.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesThe transcriptomic changes induced in the human liver cell line HepG2 by 7M of cisplatin after treatment for 12, 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesThe transcriptomic changes induced in primary mouse hepatocytes (C57BL/6 ) by 7M of cisplatin after treatment for 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View Samples