Core histone hyperacetylation impacts cooperative behavior and high-affinity binding of histone H1 to chromatin.
Linker histones stabilize higher order chromatin structures and limit access to proteins involved in DNA-dependent processes. Core histone acetylation is thought to modulate H1 binding. In the current study, we employed kinetic modeling of H1 recovery curves obtained during fluorescence recovery after photobleaching (FRAP) experiments to determine the impact of core histone acetylation on the different variants of H1. Following brief treatments with histone deacetylase inhibitor, most variants showed no change in H1 dynamics. A change in mobility was detected only when longer treatments were used to induce high levels of histone acetylation. This hyperacetylation imparted marked changes in the dynamics of low-affinity H1 population, while conferring variant-specific changes in the mobility of H1 molecules that were strongly bound. Both the C-terminal domain (CTD) and globular domain were responsible for this differential response to TSA. Furthermore, we found that neither the CTD nor the globular domain, by themselves, undergoes a change in kinetics following hyperacetylation. This led us to conclude that hyperacetylation of core histones affects the cooperative nature of low-affinity H1 binding, with some variants undergoing a predicted decrease of almost 2 orders of magnitude.
Raghuram
Nikhil
N
Department of Oncology, University of Alberta, 11560 University Avenue NW, Edmonton, Alberta, Canada T6G 1Z2.
Carrero
Gustavo
G
Stasevich
Timothy J
TJ
McNally
James G
JG
Th'ng
John
J
Hendzel
Michael J
MJ
D000107:Acetylation; D002843:Chromatin / Q000378:metabolism*; D002877:Chromosomes, Human / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D055585:Physical Phenomena; D011499:Protein Processing, Post-Translational
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones