Hierarchical Inactivation of a Synthetic Human Kinetochore by a Chromatin Modifier

被引：70

作者：

Cardinale, Stefano ^{[1
]}

Bergmann, Jan H. ^{[1
]}

Kelly, David ^{[1
]}

Nakano, Megumi ^{[2
,5
]}

Valdivia, Manuel M. ^{[3
]}

Kimura, Hiroshi ^{[4
]}

Masumoto, Hiroshi ^{[5
]}

Larionov, Vladimir ^{[2
]}

Earnshaw, William C. ^{[1
]}

机构：

[1] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland

[2] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA

[3] Univ Cadiz, Dept Bioquim & Biol Mol, Fac Ciencias, Cadiz 11510, Spain

[4] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan

[5] Kazusa DNA Res Inst, Dept Human Genome Res, Lab Cell Engn, Chiba 2920818, Japan

来源：

MOLECULAR BIOLOGY OF THE CELL | 2009年 / 20卷 / 19期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

ZINC-FINGER PROTEINS; HISTONE H3; CENP-A; CENTROMERE FUNCTION; VERTEBRATE CELLS; DNA-BINDING; HETEROCHROMATIN; COMPLEX; DOMAIN; KAP-1;

D O I：

10.1091/mbc.E09-06-0489

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We previously used a human artificial chromosome ( HAC) with a synthetic kinetochore that could be targeted with chromatin modifiers fused to tetracycline repressor to show that targeting of the transcriptional repressor tTS within kinetochore chromatin disrupts kinetochore structure and function. Here we show that the transcriptional corepressor KAP1, a downstream effector of the tTS, can also inactivate the kinetochore. The disruption of kinetochore structure by KAP1 subdomains does not simply result from loss of centromeric CENP-A nucleosomes. Instead it reflects a hierarchical disruption of the outer kinetochore, with CENP-C levels falling before CENP-A levels and, in certain instances, CENP-H being lost more readily than CENP-C. These results suggest that this novel approach to kinetochore dissection may reveal new patterns of protein interactions within the kinetochore.

引用

页码：4194 / 4204

页数：11

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