The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions

Mol Cell. 2010 Mar 26;37(6):834-42. doi: 10.1016/j.molcel.2010.01.037.


The organization of the eukaryotic genome into nucleosomes dramatically affects the regulation of gene expression. The delicate balance between transcription and DNA compaction relies heavily on nucleosome dynamics. Surprisingly, little is known about the free energy required to assemble these large macromolecular complexes and maintain them under physiological conditions. Here, we describe the thermodynamic parameters that drive nucleosome formation in vitro. To demonstrate the versatility of our approach, we test the effect of DNA sequence and H3K56 acetylation on nucleosome thermodynamics. Furthermore, our studies reveal the mechanism of action of the histone chaperone nucleosome assembly protein 1 (Nap1). We present evidence for a paradigm in which nucleosome assembly requires the elimination of competing, nonnucleosomal histone-DNA interactions by Nap1. This observation is confirmed in vivo, wherein deletion of the NAP1 gene in yeast results in a significant increase in atypical histone-DNA complexes, as well as in deregulated transcription activation and repression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • DNA / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Histones / metabolism*
  • Nucleosome Assembly Protein 1 / genetics
  • Nucleosome Assembly Protein 1 / metabolism*
  • Nucleosomes / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Thermodynamics
  • Transcription, Genetic
  • Xenopus laevis


  • Histones
  • NAP1 protein, S cerevisiae
  • Nucleosome Assembly Protein 1
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • DNA