ChIP-seq analysis workflow
Relevant ChIP-seq and associated input data sets were downloaded from publicly-available resources as listed in Supplemental Table ST1. All reads were clipped to a maximum length of 36 nucleotides (nt), then filtered to retain only sequences with a mean base quality score of at least 20. Filtered reads were aligned against the hg19 reference genome (excluding haplotype chromosomes) via Bowtie v0.12.8 with parameters “-m1 -v2” to accept only uniquely-mapped hits with a maximum of 2 mismatched bases. Multiple replicates from the same sample were merged, then duplicate reads were removed with MergeSamFiles.jar and MarkDuplicates.jar from the Picard tool suite v1.86 (http://broadinstitute.github.io/picard). For ChIP-seq data sets without an associated input sample, surrogate inputs were generated by randomly selecting 20 million uniquely-mapped, non-duplicate reads from other input data sets of the same cell type. Specifically, a surrogate U2OS input was made by downsampling the combined input data sets from DMSO, DXR, and Nutlin treatment conditions from Menendez et al., and a surrogate HCT116 input was made by downsampling the combined 5FU-treated input data sets from Botcheva and McCorkle and Wang et al. Depth tracks were generated with BEDTools genomeCoverageBed v2.17.0 and UCSC utility bedGraphToBigWig, after extending each uniquely-mapped, non-duplicate read to a length of 200 nt.
https://www.niehs.nih.gov/research/resources/databases/p53/index.cfm
Menendez, D., Nguyen, T.A., Freudenberg, J.M., Mathew, V.J., Anderson, C.W., Jothi, R. and Resnick, M.A. (2013) Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells. Nucleic Acids Res., 41, 7286-7301.
Botcheva, K. and McCorkle, S.R. (2014) Cell context dependent p53 genome-wide binding patterns and enrichment at repeats. PLoS One, 9, e113492.
Wang, B., Niu, D., Lam, T.H., Xiao, Z. and Ren, E.C. (2013) Mapping the p53 transcriptome universe using p53 natural polymorphs. Cell Death Differ., 21, 521-532.