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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53

Woojin An1, Jaehoon Kim, Robert G Roeder

  • 1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.

Cell
|June 10, 2004
PubMed

Insights

This study reveals that protein arginine methyltransferases PRMT1 and CARM1, alongside p300, are crucial for p53-dependent gene activation through direct interactions and histone modifications. These coactivators function independently and cooperatively, impacting gene expression via specific histone marks.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Transcriptional coactivators are key regulators of gene expression.
  • While often associated with histone modification, their functions can be broader.
  • Previous work highlighted the role of p300/CBP in p53 function.

Purpose of the Study:

  • To investigate the involvement of protein arginine methyltransferases (PRMTs) in p53 function.
  • To elucidate the cooperative and independent roles of p300, PRMT1, and CARM1 in p53-mediated gene activation.
  • To define the mechanisms underlying p53-dependent gene activation, including histone modifications.

Main Methods:

  • Reconstituted systems with recombinant chromatin templates and coactivators.
  • Biochemical assays to demonstrate protein interactions and enzymatic activities.
  • Chromatin immunoprecipitation (ChIP) analyses to assess coactivator and histone modification accumulation on target genes.

Main Results:

  • Identified protein arginine methyltransferases PRMT1 and CARM1 as additional factors involved in p53 function.
  • Demonstrated both independent and ordered cooperative functions of p300, PRMT1, and CARM1.
  • Confirmed mechanisms involving direct interactions with p53 and obligatory histone substrate modifications.
  • ChIP data showed ordered coactivator and histone modification accumulation on the GADD45 gene.

Conclusions:

  • p53-dependent gene activation involves diverse cofactors with distinct mechanisms.
  • Specific histone modifications are obligatory for the function of these coactivators.
  • The study defines the roles and mechanisms of p300, PRMT1, and CARM1 in p53-mediated transcriptional regulation.

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