CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells.
CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells.
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DOI：
10.1186/1756-8935-8-2
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发表时间：
2015
影响因子：
3.9
通讯作者：
Dalal Y
中科院分区：
文献类型：
--
作者：
Athwal RK;Walkiewicz MP;Baek S;Fu S;Bui M;Camps J;Ried T;Sung MH;Dalal Y
The histone H3 variant CENP-A is normally tightly regulated to ensure only one centromere exists per chromosome. Native CENP-A is often found overexpressed in human cancer cells and a range of human tumors. Consequently, CENP-A misregulation is thought to contribute to genome instability in human cancers. However, the consequences of such overexpression have not been directly elucidated in human cancer cells. To investigate native CENP-A overexpression, we sought to uncover CENP-A-associated defects in human cells. We confirm that CENP-A is innately overexpressed in several colorectal cancer cell lines. In such cells, we report that a subset of structurally distinct CENP-A-containing nucleosomes associate with canonical histone H3, and with the transcription-coupled chaperones ATRX and DAXX. Furthermore, such hybrid CENP-A nucleosomes localize to DNase I hypersensitive and transcription factor binding sites, including at promoters of genes across the human genome. A distinct class of CENP-A hotspots also accumulates at subtelomeric chromosomal locations, including at the 8q24/Myc region long-associated with genomic instability. We show this 8q24 accumulation of CENP-A can also be seen in early stage primary colorectal tumors. Our data demonstrate that excess CENP-A accumulates at noncentromeric locations in the human cancer genome. These findings suggest that ectopic CENP-A nucleosomes could alter the state of the chromatin fiber, potentially impacting gene regulation and chromosome fragility. The online version of this article (doi:10.1186/1756-8935-8-2) contains supplementary material, which is available to authorized users.
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DOI：
10.4161/nucl.23588
发表时间：
2013-01
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Bui M;Walkiewicz MP;Dimitriadis EK;Dalal Y
通讯作者：
Dalal Y
影响因子：
37.3
作者：
Amato A;Schillaci T;Lentini L;Di Leonardo A
通讯作者：
Di Leonardo A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
15.8
作者：
Chan, Timothy A.;Glockner, Sabine;Yi, Joo Mi;Chen, Wei;Van Neste, Leander;Cope, Leslie;Herman, James G.;Velculescu, Victor;Schuebel, Kornel E.;Ahuja, Nita;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A