Kinetic profiles of p300 occupancy in vivo predict common features of promoter structure and coactivator recruitment

Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11554-9. doi: 10.1073/pnas.0402156101. Epub 2004 Jul 30.

Abstract

Understanding the language encrypted in the gene regulatory regions of the human genome is a challenging goal for the genomic era. Although customary extrapolations from steady-state mRNA levels have been effective, deciphering these regulatory codes will require additional empirical data sets that more closely reflect the dynamic progression of molecular events responsible for inducible transcription. We describe an approach using chromatin immunoprecipitation to profile the kinetic occupancy of the transcriptional coactivator and histone acetyltransferase p300 at numerous mitogen-induced genes in activated T cells. Comparison of these profiles reveals a class of promoters that share common patterns of inducible expression, p300 recruitment, dependence on selective p300 domains, and sensitivity to histone deacetylase inhibitors. Remarkably, this class also shares an evolutionarily conserved promoter composition and structure that accurately predicts additional human genes with similar functional attributes. This "reverse genomic" approach will have broad application for the genome-wide classification of promoter structure and function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Computational Biology / methods*
  • Conserved Sequence
  • Gene Expression Regulation / drug effects
  • Histone Acetyltransferases
  • Humans
  • Jurkat Cells
  • Kinetics
  • Lymphocyte Activation
  • Mitogens / pharmacology
  • Promoter Regions, Genetic / genetics*
  • Promoter Regions, Genetic / physiology
  • Protein Binding / drug effects
  • Protein Transport
  • Regulatory Sequences, Nucleic Acid
  • T-Lymphocytes / metabolism
  • Transcription Factors
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Mitogens
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor