Influence of Histone Tails and H4 Tail Acetylations on Nucleosome-Nucleosome Interactions

JOURNAL OF MOLECULAR BIOLOGY

卷:414

Article

Liu, Ying¹  Lu, Chenning¹  Yang, Ye¹  Fan, Yanping¹  Yang, Renliang¹  Liu, Chuan-Fa¹  Korolev, Niko Lay¹  Nordenskioeld, Lars¹ 

[1] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore

关键词: chromatin structure;    histone modifications;    epigenetic regulation;    polyelectrolyte;    DNA condensation;   

DOI  :  10.1016/j.jmb.2011.10.031

来源: Elsevier

【 摘 要 】

Nucleosome nucleosome interaction plays a fundamental role in chromatin folding and self-association. The cation-induced condensation of nucleosome core particles (NCPs) displays properties similar to those of chromatin fibers, with important contributions from the N-terminal histone tails. We study the self-association induced by addition of cations [Mg(2+), Ca(2+), cobalt (III)hexammine(3+), spermidine(3+) and spermine(4+)] for NCPs reconstituted with wild-type unmodified histones and with globular tailless histones and for NCPs with the H4 histone tail having lysine (K) acetylations or lysine-to-glutamine mutations at positions K5, K8, K12 and K16. In addition, the histone construct with the single H4K16 acetylation was investigated. Acetylated histones were prepared by a semisynthetic native chemical ligation method. The aggregation behavior of NCPs shows a general cation-dependent behavior similar to that of the self-association of nucleosome arrays. Unlike nucleosome array self-association, NCP aggregation is sensitive to position and nature of the H4 tail modification. The tetra-acetylation in the H4 tail significantly weakens the nucleosome-nucleosome interaction, while the H4 K -> Q tetra-mutation displays a more modest effect. The single H4K16 acetylation also weakens the self-association of NCPs, which reflects the specific role of H4K16 in the nucleosome-nucleosome stacking. Tailless NCPs can aggregate in the presence of oligocations, which indicates that attraction also occurs by tail-independent nucleosome-nucleosome stacking and DNA-DNA attraction in the presence of cations. The experimental data were compared with the results of coarse-grained computer modeling for NCP solutions with explicit presence of mobile ions. (C) 2011 Elsevier Ltd. All rights reserved.

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