Regulation of the p53 transcriptional response by structurally diverse core promoters

Morachis, José M.; Murawsky, Christopher M.; Emerson, Beverly M.

doi:10.1101/gad.1856710

Cited by 86Genomics and Chromatin DynamicsCancer-related Molecular PathwaysChromatin Remodeling and Cancer

Regulation of the p53 transcriptional response by structurally diverse core promoters

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Morachis, José M., Murawsky, Christopher M., Emerson, Beverly M.·2010·Genes & Development

DOI 10.1101/gad.1856710PMC PMC2807349

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Abstract

p53 target promoters are structurally diverse and display pronounced differences in RNA polymerase II (RNAP II) occupancy even in unstressed cells, with higher levels observed on cell cycle arrest genes ( p21 ) compared with apoptotic genes ( Fas/APO1 ). This occupancy correlates well with their ability to undergo rapid or delayed stress induction. To understand the basis for such distinct temporal assembly of transcription complexes, we examined the role of core promoter structures in this process. We find that the p21 core promoter directs rapid, TATA box-dependent assembly of RNAP II preinitiation complexes (PICs), but permits few rounds of RNAP II reinitiation. In contrast, PIC formation at the Fas/APO1 core promoter is very inefficient but supports multiple rounds of transcription. We define a downstream element within the Fas/APO1 core promoter that is essential for its activation, and identify nuclear transcription factor Y (NF-Y) as its binding partner. NF-Y acts as a bifunctional transcription factor that regulates basal expression of Fas/APO1 in vivo. Thus, two critical parameters of the stress-induced p53 transcriptional response are the kinetics of gene induction and duration of expression through frequent reinitiation. These features are intrinsic, DNA-encoded properties of diverse core promoters that may be fundamental to anticipatory programming of p53 response genes upon stress.

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Target genes were reported to be activated by p53 with varying kinetics through stimulus- and promoter-specific recruitment of transcription initiation components and polymerase II.
“Target genes were reported to be activated by p53 with varying kinetics through stimulus- and promoter-specific recruitment of transcription initiation components and polymerase II.60, 61, 62, 63”
From Census and evaluation of p53 target genes (2017) · cites this paper as [61]

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Authors: Morachis, J. M., Murawsky, C. M., & Emerson, B. M.
Affiliations: Salk Institute for Biological Studies (US)
ORCID: Murawsky, Christopher M.
Emerson, Beverly M.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2009-12-29
Volume: 24
Issue: 2
Pages: 135-147
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.1856710
PMC: PMC2807349
OpenAlex: W2133832725
Cited by: 86
References: 57
Citations by year: 2025: 2 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 10 · 2019: 1 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 8
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5f31gm076953-04, CA014195)
National Cancer Institute (P30CA014195)
National Institute of General Medical Sciences (F31 GM076953, 1F31GM076953-01)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: p21, NF-Y, TATA box, downstream promoter element, apoptosis-related genes, basal transcription
MeSH terms: Amino Acid Sequence, Gene Expression Regulation, HeLa Cells, Humans, Kinetics, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Recombinant Fusion Proteins, RNA Polymerase II, Stress, Physiological, Tumor Suppressor Protein p53, TATA Box, fas Receptor, CCAAT-Binding Factor

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Regulation of the p53 transcriptional response by structurally diverse core promoters

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