A promoter-level mammalian expression atlas

Abstract

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states

“…CAGE libraries were prepared as previously described [21,65] using RNAs isolated from the nuclear fraction of the untreated/control (at 0 hour), 500 nM JQ1- and DMSO-treated H23 cells (at 3, 6, 12, and 24 hours). All of these treatment conditions have three biological replicates.…”

“…Each CAGE library was sequenced at least 15 million reads. The expression levels of genes were calculated based on the annotations from FANTOM CAT [66] as described [21]. Briefly, the numbers of CAGE read 5' ends (CAGE TSS) falling within the ±50 nt region of the prominent TSS of all CAGE clusters in FANTOM CAT were counted in all samples.…”

“…We used non-small cell lung cancer (NSCLC) cell line H23, which carries KRAS and TP53 mutations and has a mild sensitivity to BET inhibitors JQ1 and iBET [11,19,20], to assess the co-occupancy of BRD2 with hyperacetylated H4 and H3K27ac at a genome-wide level. Furthermore, we performed transcriptomics by cap-analysis of gene expression (CAGE) method [21]. CAGE captures 5' starts of transcribed RNAs, making it possible to determine precise positions of TSSs and transcribed enhancers genome-wide [21].…”

“…Furthermore, we performed transcriptomics by cap-analysis of gene expression (CAGE) method [21]. CAGE captures 5' starts of transcribed RNAs, making it possible to determine precise positions of TSSs and transcribed enhancers genome-wide [21]. Through the integrative analyses of ChIP-seq and CAGE data, we elucidate the involvement of BRD2 in gene regulation upon BET inhibition by JQ1 in H23 cells.…”

Functional annotation of the T‐cell immunoglobulin mucin family in birds

“…Murine and human TIM1 and TIM4 are immune‐related molecules, most highly expressed at the mRNA level in immune cells and lymphoid organs4, 44, 45, 46 (www.biogps.org), but with no detectable expression in non‐lymphoid tissues, except for high TIM1 expression in the kidney 2. By contrast, the chicken TIM1 and TIM4 mRNAs were highly expressed in the immune and non‐immune tissues tested.…”