XB-ART-41461Mol Cell. March 26, 2010; 37 (6): 834-42.
The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions.
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.
PubMed ID: 20347425
PMC ID: PMC2880918
Article link: Mol Cell.
Grant support: GM061909 NIGMS NIH HHS , GM067777 NIGMS NIH HHS , GM083532 NIGMS NIH HHS , Howard Hughes Medical Institute , R01 GM061909-09 NIGMS NIH HHS , R01 GM067777-07 NIGMS NIH HHS , R01 GM061909 NIGMS NIH HHS , R01 GM067777 NIGMS NIH HHS , F32 GM083532 NIGMS NIH HHS , HHMI_LUGER_K Howard Hughes Medical Institute
Genes referenced: nap1l1 napsa tab3