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Structural basis for p53 binding to its nucleosomal target DNA sequence.

Masahiro Nishimura1,2, Yoshimasa Takizawa1, Kayo Nozawa1,3

  • 1Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PNAS Nexus
|January 30, 2023
PubMed
Summary
This summary is machine-generated.

The tumor suppressor p53 protein binds to its target DNA within nucleosomes, a crucial step for gene activation. Structural studies reveal how p53 alters DNA and chromatin structure for this binding.

Keywords:
cryo-EMnucleosomep53pioneer transcription factor

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Epigenetics

Background:

  • The tumor suppressor p53 is a pioneer transcription factor.
  • p53 binds to nucleosomal DNA, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the structural mechanism of p53 binding to nucleosomal DNA.
  • To understand how p53 binding affects chromatin structure and gene activation.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) of p53-nucleosome complexes.
  • Hydroxyl radical footprinting.

Main Results:

  • p53 DNA-binding domain tetramer specifically binds p53 target DNA (p53BS) near nucleosome entry/exit.
  • p53 binding alters DNA path and detaches it from the histone surface.
  • p53 C-terminal domain interacts with linker and central nucleosomal DNA.

Conclusions:

  • Structural insights into p53-nucleosome interaction.
  • Mechanism of p53-mediated chromatin remodeling for gene activation elucidated.