Epigenetic control of mammalian centromere protein binding: does DNA methylation have a role?
Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism associated with the minor satellite DNA at its centromere. The more terminal block of satellite DNA sequences on this chromosome acts as the centromere as shown by the binding of CREST ACA serum, anti-CENP-B and anti-CENP-E polyclonal sera. Demethylation of the minor satellite DNA sequences accomplished by growing cells in the presence of the drug 5-aza-2'-deoxycytidine results in a redistribution of the CENP-B protein. This protein now binds to an enlarged area on the more terminal block and in addition it now binds to the more internal block of minor satellite DNA sequences on chromosome 1. The binding of the CENP-E protein does not appear to be affected by demethylation of the minor satellite sequences. We present a model to explain these observations. This model may also indicate the mechanism by which the CENP-B protein recognises specific sites within the arrays of minor satellite DNA on mouse chromosomes.
Mitchell
A R
AR
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Jeppesen
P
P
Nicol
L
L
Morrison
H
H
Kipling
D
D
D000818:Animals; D000906:Antibodies; D001324:Autoantigens; D002503:Centromere / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008811:Mice, Inbred DBA; D008954:Models, Biological; D011110:Polymorphism, Genetic; D011485:Protein Binding
D000906:Antibodies; D001324:Autoantigens; C497927:Cenpb protein, mouse; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; C068688:centromere protein E