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Nucleosome thermodynamics, histone modifications, and histone chaperone function
Author(s) -
Luger Karolin,
Stargell Laurie A,
Andrews Andrew J,
Chen Xu,
Zevin Alex
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.310.2
Subject(s) - nucleosome , histone , chromatosome , histone code , linker dna , microbiology and biotechnology , histone methylation , chromatin , histone h1 , chaperone (clinical) , chemistry , histone octamer , biophysics , genetics , biology , dna , biochemistry , gene expression , gene , dna methylation , medicine , pathology
Genome accessibility is regulated to a large part by the posttranslational modification of histones (PTM). Surprisingly, and despite the fact that nucleosomes were first characterized over 35 years ago, very little is known about the free energy required to assemble and maintain nucleosomes under physiological conditions, and even less is known about the effect of PTMs on nucleosome structure and stability. We have determined the structure of nucleosome bearing several PTMs, and investigated their effect on higher order structure. We also present a thermodynamic framework to describe nucleosome stability and how it is affected by histone modifications. A picture emerges in which various histone modifications have very differentiated effects on nucleosome and chromatin structure and stability, thereby fine‐tuning chromatin structure. Histone chaperones are acidic proteins that interact directly with histones and are implicated in nucleosome (dis)assembly through unknown mechanisms. We show that nucleosome assembly requires elimination of non‐nucleosomal histone‐DNA interactions through the action of the histone chaperone Nap1. Predictions from this unexpected model concur perfectly with our in vivo findings, where the absence of Nap1 results in an excess of non‐nucleosomal histone‐DNA complexes in cells. The accumulation of these atypical complexes has a dramatic effect on transcription activation and repression in vivo.