Centromeric chromatin pliability and memory at a human neocentromere.
We show that Trichostatin A (TSA)-induced partial histone hyperacetylation causes a unidirectional shift in the position of a previously defined binding domain for the centromere-specific histone H3 homologue CENP-A at a human neocentromere. The shift of approximately 320 kb is fully reversible when TSA is removed, but is accompanied by an apparent reduction in the density of CENP-A per unit length of genomic DNA at the neocentromere. TSA treatment also instigates a reversible abolition of a previously defined major domain of differentially delayed replication timing that was originally established at the neocentromeric site. None of these changes has any measurable deleterious effects on mitosis or neocentromere function. The data suggest pliability of centromeric chromatin in response to epigenetic triggers, and the non-essential nature of the regions of delayed replication for centromere function. Reversibility of the CENP-A-binding position and the predominant region of delayed replication timing following removal of TSA suggest strong memory at the original site of neocentromeric chromatin formation.
Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Melbourne, Victoria 3052, Australia.
Jeffrey M
JM
Craig
Lee H
LH
Wong
Anthony W I
AW
Lo
Elizabeth
E
Earle
K H Andy
KH
Choo
D000107:Acetylation; D000818:Animals; D001324:Autoantigens; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10; D004261:DNA Replication / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D011485:Protein Binding
D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A