The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association.
Understanding the molecular mechanisms behind regulation of chromatin folding through covalent modifications of the histone N-terminal tails is hampered by a lack of accessible chromatin containing precisely modified histones. We study the internal folding and intermolecular self-association of a chromatin system consisting of saturated 12-mer nucleosome arrays containing various combinations of completely acetylated lysines at positions 5, 8, 12 and 16 of histone H4, induced by the cations Na(+), K(+), Mg(2+), Ca(2+), cobalt-hexammine(3+), spermidine(3+) and spermine(4+). Histones were prepared using a novel semi-synthetic approach with native chemical ligation. Acetylation of H4-K16, but not its glutamine mutation, drastically reduces cation-induced folding of the array. Neither acetylations nor mutations of all the sites K5, K8 and K12 can induce a similar degree of array unfolding. The ubiquitous K(+), (as well as Rb(+) and Cs(+)) showed an unfolding effect on unmodified arrays almost similar to that of H4-K16 acetylation. We propose that K(+) (and Rb(+)/Cs(+)) binding to a site on the H2B histone (R96-L99) disrupts H4K16 ε-amino group binding to this specific site, thereby deranging H4 tail-mediated nucleosome-nucleosome stacking and that a similar mechanism operates in the case of H4-K16 acetylation. Inter-array self-association follows electrostatic behavior and is largely insensitive to the position or nature of the H4 tail charge modification.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore.
Abdollah
A
Allahverdi
Renliang
R
Yang
Nikolay
N
Korolev
Yanping
Y
Fan
Curt A
CA
Davey
Chuan-Fa
CF
Liu
Lars
L
Nordenskiöld
D000107:Acetylation; D002412:Cations / Q000737:chemistry; D002843:Chromatin / Q000737:chemistry; D003198:Computer Simulation; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D011487:Protein Conformation; D055672:Static Electricity
D002412:Cations; D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D008239:Lysine; D011188:Potassium