P53 genomic binding relative to chromatin state and histone modifications.

<p>Upper Panel: UCSC (University of California Santa Cruz, California, United States) Genome Browser view of experimental data integrated with ENCODE data. Tracks A–B (p53 genomic binding), F (gene expression fold change), H, and I are experimental data for LCLs generated in this study. Track G: ENCODE/Broad chromatin state segmentation (ChromHMM model, unstressed GM12878 cells downloaded from ENCODE). Tracks A–E display p53 ChIP-seq peaks in the <i>GDF15</i> region (e.g. orange box). Additional genome-wide information on p53 occupancy was derived from published data as described in methods. Track C: Nutlin–treated MCF7 (breast cancer cell line), Track D: 5-fluorouracil-treated MCF7, Track E: 5-fluorouracil treated IMR90 (embryonic fibroblast). Histone H3 lysine 4 tri-methylation (H3K4me3, tracks H, I) is present at an actively transcribed promoter (PGPEP1, red box) but absent (GDF15, Track I purple box) at the GDF15 promoter displaying insulating CTCF marks (CTCF, track J, blue arrow, blue box. Red box highlights the promoter region of the p53 inducible gene, PGPEP1. Numerous histone modifications align at this position and the ChromHMM track displays red indicative of an active promoter (State 1). In the region within the orange box where p53 peaks were detected, the ChromHMM track displays orange, a high degree of DNase I hypersensitivity (track K, DHS), and multiple histone modifications. Following treatment of GM12878 with DXR, tracks H and I (purple box), change in H3K4me3 marks. Track L shows placental mammalian conservation score (PhyloP). Lower Panel: Illustration of the use of the chromatin state model classification at the p53 ChIPseq maximum (p53RE) or at gene TSS for data analysis in this study.