Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 41

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Structural basis for p53 binding to its nucleosomal target DNA sequence

Nishimura, Masahiro, Takizawa, Yoshimasa, Nozawa, Kayo, Kurumizaka, Hitoshi·2022·PNAS Nexus
DOI 10.1093/pnasnexus/pgac177
Open this paper in CoChat — free account

Abstract

The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome remains elusive. Here we report the cryo-electron microscopy structures of the p53 DNA-binding domain and the full-length p53 protein complexed with a nucleosome containing the 20 base-pair target DNA sequence of p53 (p53BS). In the p53-nucleosome structures, the p53 DNA-binding domain forms a tetramer and specifically binds to the p53BS DNA, located near the entry/exit region of the nucleosome. The nucleosomal position of the p53BS DNA is within the genomic p21 promoter region. The p53 binding peels the DNA from the histone surface, and drastically changes the DNA path around the p53BS on the nucleosome. The C-terminal domain of p53 also binds to the DNA around the center and linker DNA regions of the nucleosome, as revealed by hydroxyl radical footprinting. These results provide important structural information for understanding the mechanism by which p53 binds the nucleosome and changes the chromatin structure for gene activation.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/pnasnexus/pgac177

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 45

  1. Vousden, 2009, Blinded by the light: the growing complexity of p53, Cell, 137, 413, 10.1016/j.cell.2009.04.037 · DOI · Paper page
  2. Joerger, 2008, Structural biology of the tumor suppressor p53, Annu Rev Biochem, 77, 557, 10.1146/annurev.biochem.77.060806.091238 · DOI · Paper page
  3. Luger, 1997, Crystal structure of the nucleosome core particle at 2.8 Å resolution, Nature, 389, 251, 10.1038/38444 · DOI · Paper page
  4. Neph, 2012, An expansive human regulatory lexicon encoded in transcription factor footprints, Nature, 489, 83, 10.1038/nature11212 · DOI · Paper page
  5. Zhu, 2018, The interaction landscape between transcription factors and the nucleosome, Nature, 562, 76, 10.1038/s41586-018-0549-5 · DOI · Paper page
  6. Iwafuchi-Doi, 2014, Pioneer transcription factors in cell reprogramming, Genes Dev, 28, 2679, 10.1101/gad.253443.114 · DOI · Paper page
  7. Espinosa, 2001, Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment, Mol Cell, 8, 57, 10.1016/S1097-2765(01)00283-0 · DOI · Paper page
  8. Nili, 2010, p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy, Genome Res, 20, 1361, 10.1101/gr.103945.109 · DOI
  9. Sammons, 2015, TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity, Genome Res, 25, 179, 10.1101/gr.181883.114 · DOI
  10. Laptenko, 2011, p53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation, Proc Natl Acad Sci USA, 108, 10385, 10.1073/pnas.1105680108 · DOI
  11. Yu, 2019, Defining TP53 pioneering capabilities with competitive nucleosome binding assays, Genome Res, 29, 107, 10.1101/gr.234104.117 · DOI
  12. Nishimura, 2020, Linker DNA and histone contributions in nucleosome binding by p53, J Biochem, 168, 669, 10.1093/jb/mvaa081 · DOI
  13. Kitayner, 2006, Structural basis of DNA recognition by p53 tetramers, Mol Cell, 22, 741, 10.1016/j.molcel.2006.05.015 · DOI · Paper page
  14. Weinberg, 2004, Regulation of DNA binding of p53 by its C-terminal domain, J Mol Biol, 342, 801, 10.1016/j.jmb.2004.07.042 · DOI · Paper page
  15. Scheres, 2016, Processing of Structurally Heterogeneous Cryo-EM Data in RELION, Methods in Enzymology, 579, 125, 10.1016/bs.mie.2016.04.012 · DOI · Paper page
  16. Tullius, 1986, Hydroxyl radical “footprinting”: high-resolution information about DNA-protein contacts and application to λ repressor and Cro protein, Proc Natl Acad Sci USA, 83, 5469, 10.1073/pnas.83.15.5469 · DOI · Paper page
  17. Sammons, 2020, Tumor suppressor p53: from engaging DNA to target gene regulation, Nucleic Acids Res, 48, 8848, 10.1093/nar/gkaa666 · DOI
  18. Kim, 2012, P53 requires an intact C-terminal domain for DNA binding and transactivation, J Mol Biol, 415, 843, 10.1016/j.jmb.2011.12.001 · DOI · Paper page
  19. Chen, 2021, DNA-damage-induced alternative splicing of p53, Cancers (Basel), 13, 251, 10.3390/cancers13020251 · DOI
  20. Farnung, 2017, Nucleosome-Chd1 structure and implications for chromatin remodelling, Nature, 550, 539, 10.1038/nature24046 · DOI · Paper page
  21. Ye, 2019, Structure of the RSC complex bound to the nucleosome, Science, 366, 838, 10.1126/science.aay0033 · DOI
  22. He, 2020, Structure of nucleosome-bound human BAF complex, Science, 367, 875, 10.1126/science.aaz9761 · DOI · Paper page
  23. Michael, 2020, Mechanisms of OCT4-SOX2 motif readout on nucleosomes, Science, 368, 1460, 10.1126/science.abb0074 · DOI · Paper page
  24. Hamard, 2013, The C terminus of p53 regulates gene expression by multiple mechanisms in a target- and tissue-specific manner in vivo, Genes Dev, 27, 1868, 10.1101/gad.224386.113 · DOI
  25. Vieler, 2018, P53 isoforms and their implications in cancer, Cancers (Basel), 10, 288, 10.3390/cancers10090288 · DOI
  26. Anbarasan, 2019, The emerging landscape of p53 isoforms in physiology, cancer and degenerative diseases, Int J Mol Sci, 20, 6257, 10.3390/ijms20246257 · DOI
  27. Wang, 2007, Quantitative analyses reveal the importance of regulated Hdmx degradation for P53 activation, Proc Natl Acad Sci USA, 104, 12365, 10.1073/pnas.0701497104 · DOI · Paper page
  28. Kujirai, 2018, Methods for preparing nucleosomes containing histone variants, Methods Mol Biol, 1832, 3, 10.1007/978-1-4939-8663-7_1 · DOI
  29. Kastner, 2008, GraFix: sample preparation for single-particle electron cryomicroscopy, Nat Methods, 5, 53, 10.1038/nmeth1139 · DOI · Paper page
  30. Zivanov, 2018, New tools for automated high-resolution cryo-EM structure determination in RELION-3, Elife, 7, e42166, 10.7554/eLife.42166 · DOI · Paper page
  31. Zheng, 2017, MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy, Nat Methods, 14, 331, 10.1038/nmeth.4193 · DOI · Paper page
  32. Rohou, 2015, CTFFIND4: fast and accurate defocus estimation from electron micrographs, J Struct Biol, 192, 216, 10.1016/j.jsb.2015.08.008 · DOI · Paper page
  33. Wang, 2021, Structures and implications of TBP–nucleosome complexes, Proc Natl Acad Sci USA, 118, e2108859118, 10.1073/pnas.2108859118 · DOI
  34. Goddard, 2018, UCSF ChimeraX: Meeting modern challenges in visualization and analysis, Protein Sci, 27, 14, 10.1002/pro.3235 · DOI · Paper page
  35. Croll, 2018, ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps, Acta Crystallogr Sect D Struct Biol, 74, 519, 10.1107/S2059798318002425 · DOI · Paper page
  36. Emsley, 2004, Coot: model-building tools for molecular graphics, Acta Crystallogr Sect D Biol Crystallogr, 60, 2126, 10.1107/S0907444904019158 · DOI · Paper page
  37. Afonine, 2018, Real-space refinement in PHENIX for cryo-EM and crystallography, Acta Crystallogr Sect D Struct Biol, 74, 531, 10.1107/S2059798318006551 · DOI · Paper page
  38. Liebschner, 2019, Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix, Acta Crystallogr Sect D Struct Biol, 75, 861, 10.1107/S2059798319011471 · DOI · Paper page
  39. Arimura, 2018, Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome, Nucleic Acids Res, 46, 10007
  40. Chen, 2010, Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer, Structure, 18, 246, 10.1016/j.str.2009.11.011 · DOI · Paper page
  41. Williams, 2018, MolProbity: more and better reference data for improved all-atom structure validation, Protein Sci, 27, 293, 10.1002/pro.3330 · DOI · Paper page
  42. Syed, 2010, Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome, Proc Natl Acad Sci USA, 107, 9620, 10.1073/pnas.1000309107 · DOI · Paper page
  43. Ranjan, 2015, H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast, Elife, 4, e06845, 10.7554/eLife.06845 · DOI
  44. Kujirai, 2016, Structure and function of human histone H3.Y nucleosome, Nucleic Acids Res, 44, 6127, 10.1093/nar/gkw202 · DOI
  45. Schneider, 2012, NIH Image to ImageJ: 25 years of image analysis, Nat Methods, 9, 671, 10.1038/nmeth.2089 · DOI · Paper page

Cited by

See all 41

Metadata

Authors
Nishimura, M., Takizawa, Y., Nozawa, K., & Kurumizaka, H.
Affiliations
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
ORCID
Venue
PNAS Nexus
Publisher
Oxford University Press (OUP)
Published
2022-09-01
Volume
1
Issue
4
ISSN
2752-6542
DOI
10.1093/pnasnexus/pgac177
Cited by
41
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor, 3 d)
Funders
  • Japan Society for the Promotion of Science (JP19J23094, JP19K06522, JP18H05534, JP20H00449, JP20K06599, JP21H05154)
  • Japan Agency for Medical Research and Development (JP21am0101076, JP22ama121009)
  • Precursory Research for Embryonic Science and Technology (JPMJPR18K9)
  • Exploratory Research for Advanced Technology (JPMJER1901)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Structural basis for p53 binding to its nucleosomal target DNA sequence. https://app.cochat.ai/papers/10.1093/pnasnexus/pgac177
The paper
Nishimura, M., Takizawa, Y., Nozawa, K., & Kurumizaka, H. (2022). Structural basis for p53 binding to its nucleosomal target DNA sequence. PNAS Nexus. https://doi.org/10.1093/pnasnexus/pgac177

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.