Histone hyperacetylation can induce unfolding of the nucleosome core particle.
A direct correlation exists between the level of histone H4 hyperacetylation induced by sodium butyrate and the extent to which nucleosomes lose their compact shape and become elongated (62.0% of the particles have a length/width ratio over 1.6; overall mean in the length/width ratio = 1.83 +/- 0.48) when bound to electron microscope specimen grids at low ionic strength (1mM EDTA, 10mM Tris, pH 8.0). A marked proportion of elongated core particles is also observed in the naturally occurring hyperacetylated chicken testis chromatin undergoing spermatogenesis when analyzed at low ionic strength (36.8% of the particles have a length/width ratio over 1.6). Core particles of elongated shape (length/width ratio over 1.6) generated under low ionic strength conditions are absent in the hypoacetylated chicken erythrocyte chromatin and represent only 2.3% of the untreated Hela S3 cell core particles containing a low proportion of hyperacetylated histones. The marked differences between control and hyperacetylated core particles are absent if the particles are bound to the carbon support film in the presence of 0.2 M NaCl, 6mM MgCl2 and 10mM Tris pH 8.0, conditions known to stabilize nucleosomes. A survey of the published work on histone hyperacetylation together with the present results indicate that histone hyperacetylation does not produce any marked disruption of the core particle 'per se', but that it decreases intranucleosomal stabilizing forces as judged by the lowered stability of the hyperacetylated core particle under conditions of shearing stress such as cationic competition by the carbon support film of the EM grid for DNA binding.
Oliva
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R
Department of Medical Biochemistry, Faculty of Medicine, University of Calgary, Alberta, Canada.
Bazett-Jones
D P
DP
Locklear
L
L
Dixon
G H
GH
D000107:Acetylation; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002645:Chickens; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009707:Nucleosomes / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism
D002087:Butyrates; D006657:Histones; D009707:Nucleosomes; D020148:Butyric Acid