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

Epigenetics & Chromatin
Rajbir K AthwalYamini Dalal

Abstract

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. O...Continue Reading

References

Feb 1, 1986·The Journal of Clinical Investigation·W EarnshawN Rothfield
Apr 1, 1987·The Journal of Cell Biology·D K PalmerR L Margolis
Jul 22, 1998·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·T L Bailey, M Gribskov
Jan 19, 1999·Methods in Cell Biology·A Van Hooser, W R Brinkley
Jan 19, 2000·Nature·B D Strahl, C D Allis
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·K YodaT Okazaki
Nov 22, 2000·The Journal of Cell Biology·R D ShelbyK F Sullivan
Mar 7, 2002·Developmental Cell·Michael D BlowerGary H Karpen
Aug 10, 2002·Journal of Cellular and Molecular Medicine·N C Popescu, D B Zimonjic
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ai Leen LamBeth A Sullivan
Apr 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Takehito FuruyamaSteven Henikoff
Dec 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ian K GreavesDavid J Tremethick
Feb 27, 2007·PLoS Genetics·M Katharine RuddBarbara J Trask
Mar 7, 2007·The Journal of Cell Biology·Lars E T JansenDon W Cleveland
Jun 19, 2007·Genes & Development·Chunyuan Jin, Gary Felsenfeld
Jun 22, 2007·Nature·Jessica A DownsAndré Nussenzweig
Aug 7, 2007·PLoS Biology·Yamini DalalSteven Henikoff
Mar 18, 2008·Molecular Cell·Sam JohnGordon L Hager
Nov 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rajbir K GillJin Jen
May 5, 2009·Cell·Daniel R FoltzDon W Cleveland
May 5, 2009·Cell·Elaine M DunleavyGeneviève Almouzni-Pettinotti
Jul 25, 2009·The EMBO Journal·Stefano Santaguida, Andrea Musacchio
Sep 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Samantha G ZeitlinDon W Cleveland
Dec 17, 2009·Molecular Cancer·Angela AmatoAldo Di Leonardo
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Muhammad ShuaibAli Hamiche
Feb 19, 2010·Nature·Rameen BeroukhimMatthew Meyerson
Jul 24, 2010·Human Molecular Genetics·Gayane AmbartsumyanAmander T Clark
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Emilios K DimitriadisYamini Dalal
Nov 13, 2010·Molecular Cell·Geetha HewawasamJennifer L Gerton
Dec 31, 2010·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Sarah L Thompson, Duane A Compton
Jan 25, 2011·Nature Genetics·Sam JohnJohn A Stamatoyannopoulos
Feb 16, 2011·The Journal of Cell Biology·Rafael BernadAna Losada
Mar 1, 2011·Current Biology : CB·Emanuela ScrepantiAndrea Musacchio
Apr 13, 2011·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Lori L SullivanBeth A Sullivan

❮ Previous
Next ❯

Citations

Aug 12, 2015·Genes·Daniël P MeltersYamini Dalal
Feb 2, 2016·Current Opinion in Genetics & Development·Lisa-Maria Zink, Sandra B Hake
Dec 10, 2015·Epigenomics·L Ashley WatsonNathalie G Bérubé
Mar 24, 2016·Cellular Oncology (Dordrecht)·Angelo Ferraro
May 10, 2015·Current Opinion in Genetics & Development·Florian A Steiner, Steven Henikoff
Jun 4, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Lucas A SalasCristina M Villanueva
Apr 12, 2016·International Journal of Cancer. Journal International Du Cancer·Xia SunSifeng Qu
Sep 2, 2016·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Lori L SullivanBeth A Sullivan
Dec 8, 2016·Nature Reviews. Molecular Cell Biology·Paul B Talbert, Steven Henikoff
Mar 31, 2017·Genes & Development·Dan FilipescuGeneviève Almouzni
Dec 4, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Steven HenikoffPaul B Talbert
Dec 28, 2018·Nucleic Acids Research·Abhishek Bharadwaj SharmaEric Van Dyck
Mar 10, 2018·Nucleic Acids Research·Geetha S HewawasamJennifer L Gerton
Nov 13, 2019·Nucleic Acids Research·Engin DemirdizenSylvia Erhardt
Apr 17, 2020·G3 : Genes - Genomes - Genetics·Jessica R EisenstattMunira A Basrai
Mar 24, 2018·Chromosoma·Shashank Srivastava, Daniel R Foltz
Feb 27, 2018·F1000Research·Jonathan NyeYamini Dalal
Jan 11, 2019·Frontiers in Genetics·Ksenia Smurova, Peter De Wulf
Aug 4, 2019·Scientific Reports·Anjan K SahaRafael Contreras-Galindo
May 7, 2020·The Journal of Biological Chemistry·Anjan K SahaDavid M Markovitz
Nov 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Daniël P MeltersYamini Dalal
Aug 14, 2020·Genes·Ganesan Arunkumar, Daniël P Melters
Dec 28, 2017·Genetics·Gemma MacchiaClelia Tiziana Storlazzi
Sep 28, 2018·The Journal of Cell Biology·Shweta MendirattaGenevieve Almouzni
Nov 30, 2019·Chromosoma·Yick Hin LingKaren Wing Yee Yuen
Feb 3, 2020·Cellular and Molecular Life Sciences : CMLS·Charmaine Yan Yu WongKaren Wing Yee Yuen
Aug 10, 2016·Cold Spring Harbor Perspectives in Medicine·Steven Henikoff
Feb 13, 2019·Nucleic Acids Research·Olga Moreno-MorenoFernando Azorin
Jul 28, 2020·Genes·Megan A Mahlke, Yael Nechemia-Arbely
Mar 4, 2020·Cells·Mary PitmanYamini Dalal
Nov 11, 2020·Cells·Juliette FerrandSophie E Polo

❮ Previous
Next ❯

Methods Mentioned

BETA
atomic force microscopy
PCR
immunoprecipitation
immunoprecipitations
AFM
chips
ChIP-seq
ChIP
salt dialysis
immunoprecipitation-seq

Software Mentioned

CASAVA
Studio
Image J
Bio
ENCODE
TOMTOM
NIH Image J
Agilent 2100 Expert
MEME
SigmaPlot

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.