Abstract
The nature of the structural changes induced by histone acetylation at the different levels of chromatin organization has been very elusive. At the histone level, it has been proposed on several occasions that acetylation may induce an alpha-helical conformation of their acetylated N-terminal domains (tails). In an attempt to provide experimental support for this hypothesis, we have purified and characterized the tail of histone H4 in its native and mono-, di-, tri-, and tetra- acetylated form. The circular dichroism analysis of these peptides shows conclusively that acetylation does increase their alpha-helical content. Furthermore, the same spectroscopic analysis shows that this is also true for both the acetylated nucleosome core particle and the whole histone octamer in solution. In contrast to the native tails in which the alpha-helical organization appears to be dependent upon interaction of these histone regions with DNA, the acetylated tails show an increase in alpha-helical content that does not depend on such an interaction.
Highlights
The identification of histone acetyltransferases as integral components of transcriptional eukaryotic complexes [1] has renewed interest in histone acetylation; the precise structural role of this important post-translational modification remains elusive
In an attempt to determine if the ␣-helical conformation of the tails is a result of their interaction with the nucleosomal DNA as it has been routinely hypothesized [13], we looked at the ionic strength variation of the spectrum of native nucleosome core particles in the range of 25– 600 mM NaCl
The Tails of the Histones Adopt an ␣-Helical Conformation upon Binding to DNA in the Nucleosome—The value of 48.7% for the ␣-helical content of the histone octamer in solution as determined from the CD spectrum is in surprisingly good agreement with the value of 49.4% determined from the crystal structure [34]
Summary
The identification of histone acetyltransferases as integral components of transcriptional eukaryotic complexes [1] has renewed interest in histone acetylation; the precise structural role of this important post-translational modification remains elusive. The acetylated particle adopts a more asymmetric structure [5] This is mainly the result of the DNA ends flanking this chromatin particle binding less tightly to the histones and adopting a stretched conformation [2, 6]. As ionic strength is increased, acetylated histone tails are more readily released from DNA interaction(s) [7] than their nonacetylated counterparts This is as expected and is a consequence of the charge neutralization resulting from acetylation. It has been recently postulated that the spacing of the acetylatable lysine residues of the H3-H4 histone tails is “reminiscent of that of an ␣ -helix” [12] This is an idea first proposed 30 years ago by Sung and Dixon [19]. This paper represents the first experimental evidence that such a postulate is correct
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