Transcriptional outcomes and kinetic patterning of gene expression in response to NF-κB activation
Fig 4
Repression of gene expression by NF-κB.
Genes whose expression was increased by dnIκBα in both Tet-responsive clones were identified by RNA-Seq. (A) Genes that bound RELA (middle, green) and their time-dependent expression patterns in the absence (blue) or presence (green) of Tet-induced dnIκBα are shown on the right. See also S4A Fig. The letters “Rd” after a pattern number indicate genes that were down-regulated by RELA binding, and the letters “Ri” indicate genes whose down-regulation was RELA dependent but did not bind RELA. Numbers of genes in each category are shown in black below the graphs. Red numbers correspond to genes whose expression changed more than 2-fold in the absence of Tet. Expression patterns of 178 dnIκBα-up-regulated genes that did not bind RELA (middle, gray) are shown on the left, with numbers and color coding as described above. (B) Representative examples of dnIκBα-up-regulated genes that bind RELA. Top 2 tracks show RNA-Seq tracks in the presence or absence of Tet-induced dnIκBα at the time of maximal RNA expression; the y axis denotes normalized reads per million. Complete time courses for each gene are provided in S4B Fig. The bottom part shows RELA ChIP-Seq tracks over the entire time course in activated BJAB cells. Genomic organization and transcription orientation (arrows) are shown below the input DNA track. Numbers above the tracks refer to gene location in hg19. The y axis denotes normalized reads per 10 million. (C) Representative examples of dnIκBα-up-regulated genes that do not bind RELA. These genes are proposed to be modulated by RELA-responsive factors (see text). RNA-Seq tracks over the complete activation time course in the absence (-Tet) or presence (+Tet) of dnIκBα are shown. Genome scale datasets are available on the GEO website (http://www.ncbi.nlm.nih.gov/geo/) (Accession number GSE117259). ChIP-Seq, chromatin immunoprecipitation and sequencing; dnIκBα, dominant negative NFKB inhibitor alpha; GEO, Gene Expression Omnibus; NF-κB, nuclear factor kappa B; RNA-Seq, RNA sequencing; Tet, tetracycline.