Locally acting transcription factors regulate p53-dependent cis-regulatory element activity

Nucleic Acids Research
Allison N CatizoneMorgan A Sammons

Abstract

The master tumor suppressor p53 controls transcription of a wide-ranging gene network involved in apoptosis, cell cycle arrest, DNA damage repair, and senescence. Recent studies revealed pervasive binding of p53 to cis-regulatory elements (CREs), which are non-coding segments of DNA that spatially and temporally control transcription through the combinatorial binding of local transcription factors. Although the role of p53 as a strong trans-activator of gene expression is well known, the co-regulatory factors and local sequences acting at p53-bound CREs are comparatively understudied. We designed and executed a massively parallel reporter assay (MPRA) to investigate the effect of transcription factor binding motifs and local sequence context on p53-bound CRE activity. Our data indicate that p53-bound CREs are both positively and negatively affected by alterations in local sequence context and changes to co-regulatory TF motifs. Our data suggest p53 has the flexibility to cooperate with a variety of transcription factors in order to regulate CRE activity. By utilizing different sets of co-factors across CREs, we hypothesize that global p53 activity is guarded against loss of any one regulatory partner, allowing for dynamic and r...Continue Reading

References

Apr 1, 1992·Nature Genetics·W S el-DeiryB Vogelstein
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·E SetoT Shenk
May 29, 2000·Trends in Genetics : TIG·P RiceA Bleasby
Aug 29, 2001·Nature Structural Biology·A AyedC H Arrowsmith
Jun 5, 2002·Genome Research·W James KentDavid Haussler
Dec 9, 2003·Development·Meghana M Kulkarni, David N Arnosti
Dec 19, 2003·Nucleic Acids Research·Donna KarolchikW James Kent
Jan 6, 2004·Science·Lyubomir T VassilevEmily A Liu
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Apr 29, 2006·Nature Genetics·Piero CarninciYoshihide Hayashizaki
May 12, 2006·Genome Research·Martin C FrithAlbin Sandelin
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Nov 18, 2010·Bioinformatics·Simon J van Heeringen, Gert Jan C Veenstra
Nov 1, 2011·Nature Methods·John S Reece-HoyesAlbertha J M Walhout
Nov 8, 2011·Genes & Development·Kenneth S Zaret, Jason S Carroll
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Aug 8, 2012·Nature Reviews. Genetics·François Spitz, Eileen E M Furlong
Sep 8, 2012·Nature·Robert E ThurmanJohn A Stamatoyannopoulos
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 22, 2013·Cell·Arttu JolmaJussi Taipale
Mar 7, 2014·Nature Structural & Molecular Biology·Edwin Smith, Ali Shilatifard
Mar 13, 2014·Nature Reviews. Genetics·Daria ShlyuevaAlexander Stark
Mar 25, 2014·Molecular Cell·Hans-Martin HerzAli Shilatifard
Mar 29, 2014·Nature·Robin AnderssonAlbin Sandelin
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Dec 9, 2014·Cell Cycle·Martin FischerKurt Engeland
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Apr 25, 2015·Cell·Juan I Fuxman BassAlbertha J M Walhout

❮ Previous
Next ❯

Citations

Aug 17, 2020·Nucleic Acids Research·Morgan A SammonsMartin Fischer
Jan 15, 2021·Nucleic Acids Research·Alon SenitzkiTali E Haran

❮ Previous
Next ❯

Datasets Mentioned

BETA
HCT116
GSE53966
GSE86165
1
GSE137297

Methods Mentioned

BETA
Assay
PCR
Illumina sequencing
transfection
RNA-seq
ChIP
ChIP-seq
immunoprecipitation
Electrophoretic
amplicon sequencing

Key Resources (RRID) Mentioned

A

Software Mentioned

HOMER
PhyloP
STAR
hisat2
DESeq2
FastX
- toolkit
liftOver
deepTools
p53scan

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis