Articles producció científica> Medicina i Cirurgia

CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells

  • Identification data

    Identifier: imarina:9298018
    Authors:
    Athwal, Rajbir K.Walkiewicz, Marcin P.Baek, SongjoonFu, SongBui, MinhCamps, JordiRied, ThomasSung, Myong-HeeDalal, Yamini
    Abstract:
    Background: 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.Results: 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.Conclusions: 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.
  • Others:

    Author, as appears in the article.: Athwal, Rajbir K.; Walkiewicz, Marcin P.; Baek, Songjoon; Fu, Song; Bui, Minh; Camps, Jordi; Ried, Thomas; Sung, Myong-Hee; Dalal, Yamini;
    Department: Medicina i Cirurgia
    URV's Author/s: Camps Andreu, Jorge
    Keywords: Myc gene I-hypersensitive sites Histone h3 variant Glucocorticoid-receptor E3 ubiquitin ligase Dna Crystal-structure Chromatin requires Centromere protein-a C-myc
    Abstract: Background: 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.Results: 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.Conclusions: 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.
    Thematic Areas: Molecular biology Genetics & heredity Genetics
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: jorge.camps@urv.cat
    Author identifier: 0000-0002-3165-3640
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/1756-8935-8-2
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Epigenetics & Chromatin. 8
    APA: Athwal, Rajbir K.; Walkiewicz, Marcin P.; Baek, Songjoon; Fu, Song; Bui, Minh; Camps, Jordi; Ried, Thomas; Sung, Myong-Hee; Dalal, Yamini; (2015). CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells. Epigenetics & Chromatin, 8(), -. DOI: 10.1186/1756-8935-8-2
    Article's DOI: 10.1186/1756-8935-8-2
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2015
    Publication Type: Journal Publications
  • Keywords:

    Genetics,Genetics & Heredity,Molecular Biology
    Myc gene
    I-hypersensitive sites
    Histone h3 variant
    Glucocorticoid-receptor
    E3 ubiquitin ligase
    Dna
    Crystal-structure
    Chromatin requires
    Centromere protein-a
    C-myc
    Molecular biology
    Genetics & heredity
    Genetics
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