the role of histone h4 biotinylation in the structure of nucleosomes组蛋白h4生物素酰化作用的核小体的结构.pdfVIP

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes 1 2 4 4 3 2 Nina A. Filenko , Carol Kolar , John T. West , S. Abbie Smith , Yousef I. Hassan , Gloria E. O. Borgstahl , 3 1 Janos Zempleni , Yuri L. Lyubchenko * 1 Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America, 2 The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America, 3 Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, Nebraska, United States of America, 4 The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America Abstract Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp t