CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells
Rajbir K Athwal,Marcin P. Walkiewicz,Songjoon Baek,Song Fu,Minh Bui,Jordi Camps,Thomas Ried,Myong-Hee Sung,Yamini Dalal +8 more
TLDR
These findings suggest that ectopic CENP-A nucleosomes could alter the state of the chromatin fiber, potentially impacting gene regulation and chromosome fragility.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.read more
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Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores
TL;DR: Karpen et al. as discussed by the authors showed that overexpressed CID is mislocalized into normally non-centromeric regions in Drosophila tissue culture cells and animals, and showed that mitotic delays, anaphase bridges, chromosome fragmentation, and cell and organismal lethality are all direct consequences of mislocalization.
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Interaction of the Glucocorticoid Receptor with the Chromatin Landscape
Gordon L. Hager,Pete J. Sabo,Robert E. Thurman,John A. Stamatoyannopoulos,Myong-Hee Sung,Simon C. Biddie,Sam John +6 more
TL;DR: In this article, the authors characterized glucocorticoid receptor (GR) binding events and chromatin structural transitions across GR-induced or -repressed genes, revealing that GR binding invariably occurs at nuclease-accessible sites (DHS).
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Histone variants on the move: substrates for chromatin dynamics
Paul B. Talbert,Steven Henikoff +1 more
TL;DR: The dynamic processes by which particular histone variants become substrates of histone chaperones, ATP-dependent chromatin remodellers and histone-modifying enzymes are reviewed.
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The CENP-L-N Complex Forms a Critical Node in an Integrated Meshwork of Interactions at the Centromere-Kinetochore Interface.
TL;DR: It is found that the CCAN does not assemble as a linear hierarchy, and instead, each sub-complex requires multiple non-redundant interactions for its localization to centromeres and the structural integrity of the overall assembly.
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Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells
Roshan L. Shrestha,Grace S. Ahn,Mae I. Staples,Kizhakke Mattada Sathyan,Tatiana S. Karpova,Daniel R. Foltz,Munira A. Basrai +6 more
TL;DR: It is established that CENP-A overexpression and mislocalization result in a CIN phenotype in human cells, and depletion of histone chaperone DAXX prevents CENp-A mis localization and rescues the reduced interkinetochore distance and C IN phenotype in C ENP- A overexpressing cells.
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c-Myc Is a Universal Amplifier of Expressed Genes in Lymphocytes and Embryonic Stem Cells
Zuqin Nie,Gangqing Hu,Gang Wei,Kairong Cui,Arito Yamane,Wolfgang Resch,Ruoning Wang,Douglas R. Green,Lino Tessarollo,Rafael Casellas,Keji Zhao,David Levens +11 more
TL;DR: To observe Myc target expression and function in a system where Myc is temporally and physiologically regulated, the transcriptomes and the genome-wide distributions of Myc, RNA polymerase II, and chromatin modifications were compared during lymphocyte activation and in ES cells as well.
Journal ArticleDOI
Chromatin accessibility pre-determines glucocorticoid receptor binding patterns
Sam John,Peter J. Sabo,Robert E. Thurman,Myong-Hee Sung,Simon C. Biddie,Thomas A. Johnson,Gordon L. Hager,John A. Stamatoyannopoulos +7 more
TL;DR: Up to 95% of de novo genomic binding by the glucocorticoid receptor, a paradigmatic ligand-activated transcription factor, is targeted to preexisting foci of accessible chromatin, defining a framework for understanding regulatory factor–genome interactions and providing a molecular basis for the tissue selectivity of steroid pharmaceuticals and other agents that intersect the living genome.