human p53 Binding And Expression Resource (BAER) hub

Description of main hub

The transcriptional networks influenced by the p53 tumor suppressor are well-characterized in many organisms. However, a global understanding of requirements for in vivo interactions between the p53 transcription factor and DNA along with transcriptional relationships across human biological systems in response to various p53 activating situations remains limited. Using a common analysis pipeline, we analyzed 41 data sets from genome-wide ChIP-seq studies of which 16 have associated gene expression data. The resulting extensive analysis, accessible at the p53 BAER hub via the UCSC browser, provides a robust platform to characterize p53 binding throughout the human genome including direct influence on gene expression and underlying mechanisms. We establish the impact of spacers and mismatches from consensus on p53 binding in vivo and propose that once bound, neither significantly influences the likelihood of expression. Our rigorous approach revealed a large p53 genome-wide cistrome composed of >900 genes directly targeted by p53. Importantly, we identify a core cistrome signature composed of genes appearing in over half the data sets, and we identify signatures that are treatment- and/or cell-specific, demonstrating new functions for p53 in cell biology. Our analysis reveals a broad homeostatic role for human p53 that is relevant to both basic and translational studies.

Data Statistics

This set of data tracks represents a comprehensive compilation of the human p53 transcription factor binding sites based on ChIP-seq and gene expression experiments generated by various labs. The tracks represent peak calls and signals that were generated based on a uniform processing pipeline of all published raw data. Included in the data sets are results from 13 cell types and 12 methods of inducing or activating p53 that span nine timepoints (from 1 to 48 hr after treatment).

Display Conventions and Configuration

The default displays the p53 activated ChIP-seq tracks and peaks and their corresponding inputs tracks. Gene expression calls for the 16 data sets that contain both ChIP-seq and expression data are also displayed. Tracks of other regulatory elements (microRNA, lincRNA, FANTOM5 enhancers, G-quadruplex, and CpG Islands) are displayed as well. Control, non-activated p53 ChIP-seq data can be visualized as an additional composite track. The individual ChIP-seq tracks are organized by cell and condition by which p53 is induced or activated, where samples can be selected from a cell vs. condition matrix. Each track can be turned on/off individually.

The colors for each classification are as follows:

coverage track depth
SISSRs peak calls
p53 peaks in 2+ data sets
p53 peaks in 20+ data sets
Non-coding RNA (microRNA, lincRNA, enhancer RNA)
G-quadruplex structures
CpG Islands
p53 perfect 20mer motif
p53 cistrome target genes
transcriptome in 2+ data sets
upregulated DEG
downregulated DEG
no change in expression

Credit

These data were analyzed by Nguyen et al., at the National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS) in Research Triangle Park, North Carolina, USA. Please direct all questions to menendez@niehs.nih.gov.

https://www.niehs.nih.gov/research/resources/databases/p53/index.cfm

References

Nguyen TT, Grimm SA, Bushel PR, Li J, Li Y, Bennett BD, Lavender CA, Ward JM, Fargo DC, Anderson CW, Li L, Resnick MA, Menendez D. Revealing a human p53 universe. Nucleic Acids Res. 2018;46:8153-8167