A 330 kb CENP-A binding domain and altered replication timing at a human neocentromere

被引：110

作者：

Lo, AWI ^{[1
]}

Craig, JM ^{[1
]}

Saffery, R ^{[1
]}

Kalitsis, P ^{[1
]}

Irvine, DV ^{[1
]}

Earle, E ^{[1
]}

Magliano, DJ ^{[1
]}

Choo, KHA ^{[1
]}

机构：

[1] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia

来源：

EMBO JOURNAL | 2001年 / 20卷 / 08期

关键词：

CENP-A; centromere; chromatin; neocentromere; replication timing;

D O I：

10.1093/emboj/20.8.2087

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Centromere protein A (CENP-A) is an essential centromere-specific histone H3 homologue, Using combined chromatin immunoprecipitation and DNA array analysis, we have defined a 330 kb CENP-A binding domain of a 10q25.3 neocentromere found on the human marker chromosome mardel (10), This domain is situated adjacent to the 80 kb region identified previously as the neocentromere site through lower-resolution immunofluorescence/FISH analysis of metaphase chromosomes. The 330 kb CENP-A binding domain shows a depletion of histone H3, providing evidence for the replacement of histone H3 by CENP-A within centromere-specific nucleosomes. The DNA within this domain has a high AT-content comparable to that of alpha -satellite, a high prevalence of LINEs and tandem repeats, and fewer SINEs and potential genes than the surrounding region. FISH analysis indicates that the normal 10q25.3 genomic region replicates around mid-S phase, Neoceutromere formation is accompanied by a replication time lag around but not within the CENP-A binding region, with this lag being significantly more prominent to one side. The availability of fully sequenced genomic markers makes human neocentromeres a powerful model for dissecting the functional domains of complex higher eukaryotic centromeres.

引用

页码：2087 / 2096

页数：10

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