|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Histone Structures: Targets for Modifications by Molecular Assemblies
bBiology and Medicine College, Council for the Central Laboratories of the Research Councils Daresbury Laboratory, Warrington, Cheshire WA4 4AD, United Kingdom cSchool of Biomolecular Sciences, John Moores University, Liverpool L3 3AF, United Kingdom dStructural Biology, Galderma R&D, BP 87F-06902 Sophia Antipolis, Cedex, France
aAddress for correspondence: James M. Nicholson, Biology and Medicine College, CCLRC Daresbury Laboratory, Warrington, Cheshire WA4 4AD, U.K. Voice: +44-1925-603905; fax: +44-1925-603124. e-mail: j.m.nicholson{at}dl.ac.uk
The core histone proteins contain modification sites that are key elements in the regulation of the cell cycle, DNA replication and repair with histone assembly, control of gene expression, and transcriptional elongation. Much work has been done on the various molecular assemblies that remodel nucleosomes, methylate, ubiquitinate, and cause ADP-ribosylation of histones, and acetylate and phosphorylate core histone tails. The core histones are the final targets of the enzymes in the molecular assemblies. What structural changes in the histones are correlated with these modifications? This paper considers the high-resolution structure of the histone octamer and stresses the importance of histone docking sequences in the binding of the two (H2A-H2B) dimers to the (H3-H4)2 tetramer. There is an extensive acid-base area of interaction between histone octamers in crystals at high salt, which may have implications for nucleosome remodeling. We show that there are regions of high
 -helix probability in all core histone N-terminal tails in regions where lysine acetylation occurs. There are also consensus sequences spanning up to eight amino acid residues between some histone tail regions. Circular dichroism studies using synchrotron radiation at wavelengths as low as 130 nm are promising for the accurate measurement of changes of histone secondary structure related to function.
Key Words: chromatin • histone octamer • linker histones • crystallography • docking sequences • remodeling • helix probability • circular dichroism
|
 |
 |
