BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells

Nature
David N DebruyneRani E George

Abstract

The CCCTC-binding factor (CTCF), which anchors DNA loops that organize the genome into structural domains, has a central role in gene control by facilitating or constraining interactions between genes and their regulatory elements1,2. In cancer cells, the disruption of CTCF binding at specific loci by somatic mutation3,4 or DNA hypermethylation5 results in the loss of loop anchors and consequent activation of oncogenes. By contrast, the germ-cell-specific paralogue of CTCF, BORIS (brother of the regulator of imprinted sites, also known as CTCFL)6, is overexpressed in several cancers7-9, but its contributions to the malignant phenotype remain unclear. Here we show that aberrant upregulation of BORIS promotes chromatin interactions in ALK-mutated, MYCN-amplified neuroblastoma10 cells that develop resistance to ALK inhibition. These cells are reprogrammed to a distinct phenotypic state during the acquisition of resistance, a process defined by the initial loss of MYCN expression followed by subsequent overexpression of BORIS and a concomitant switch in cellular dependence from MYCN to BORIS. The resultant BORIS-regulated alterations in chromatin looping lead to the formation of super-enhancers that drive the ectopic expression of ...Continue Reading

Associated Datasets

References

Jan 1, 1989·Cancer Chemotherapy and Pharmacology·M M Tomayko, C P Reynolds
Apr 1, 1986·Cancer Genetics and Cytogenetics·J Whang-PengM A Israel
Aug 23, 2002·Seminars in Cancer Biology·Elena M KlenovaVictor V Lobanenkov
Feb 13, 2004·Bioinformatics·Laurent GautierRafael A Irizarry
Sep 6, 2005·Trends in Neurosciences·Michael Wegner, C Claus Stolt
Dec 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Anna V GalkinMarkus Warmuth
May 24, 2008·Science·Yasemin SancakDavid M Sabatini
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kristen L MeerbreyStephen J Elledge
Oct 25, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Irena Martin-Kleiner
Oct 30, 2012·Cell·Jakob LovénRichard A Young
May 25, 2013·Nature Reviews. Cancer·Nai-Kong V Cheung, Michael A Dyer
May 28, 2013·Cell·Jennifer E Phillips-CreminsVictor G Corces
Oct 15, 2013·Cell·Denes HniszRichard A Young
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
May 12, 2015·The Journal of Molecular Diagnostics : JMD·Shuguang HuangVictoria Plamadeala
Jun 9, 2015·Nature Genetics·Riku KatainenLauri A Aaltonen
Oct 27, 2015·Proceedings of the National Academy of Sciences of the United States of America·Adrian L SanbornErez Lieberman Aiden
Dec 2, 2015·Genome Biology·Nicolas ServantEmmanuel Barillot
Dec 22, 2015·Cell Stem Cell·Xiong JiRichard A Young
Dec 25, 2015·Nature·William A FlavahanBradley E Bernstein
Mar 5, 2016·Science·Denes HniszRichard A Young
Jan 17, 2017·Nature Communications·Grace X Y ZhengJason H Bielas
Dec 26, 2017·Cell Chemical Biology·Yang GaoRani E George
Mar 17, 2018·Brain Research·Daniel J DennisCarol Schuurmans
Apr 7, 2018·Science·Matthias MuharJohannes Zuber

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Citations

Jan 14, 2020·Cancer Metastasis Reviews·Gian Paolo Tonini, Mario Capasso
Sep 18, 2020·Nucleic Acids Research·Yuliang Feng, Siim Pauklin
May 13, 2020·Genome Biology·Mayilaadumveettil NishanaJane A Skok
Jun 25, 2020·Japanese Journal of Clinical Oncology·Yusuke SuenagaAkira Nakagawara
Sep 26, 2020·The Journal of Clinical Endocrinology and Metabolism·Matthew D Ringel
Jan 17, 2021·Protein & Cell·Yuliang FengSiim Pauklin
Oct 30, 2020·International Journal of Molecular Sciences·Evgeniya OshchepkovaNikolay Kolchanov
Nov 5, 2020·British Journal of Cancer·Saroor A PatelSakari Vanharanta
Jan 1, 2020·RNA Biology·Yan HuangXiangting Wang
Dec 6, 2020·Journal of Hematology & Oncology·Mingye HongHua Zhang
Mar 24, 2021·Tissue & Cell·Leyla SatiJames McGrath
Nov 7, 2020·Nature Communications·Elphège P NoraBenoit G Bruneau
May 3, 2021·Oncogene·Laia RichartRaphaël Margueron
Jun 24, 2021·Nature Communications·Samuel Rivero-HinojosaVictor V Lobanenkov
May 6, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johannes H Schulte, Angelika Eggert
Apr 22, 2021·Cancer Discovery·Amy C MandigoKaren E Knudsen
Sep 14, 2021·Frontiers in Cell and Developmental Biology·Tao WangJinjian Yang
Sep 18, 2021·Cancer Research·Narendra Wajapeyee, Romi Gupta

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Methods Mentioned

BETA
scRNA-seq
immunoprecipitation
Assay
Protein Assay
transfection
PCR
xenograft
ChIP
Hi-C
HiChIP

Software Mentioned

Fastqc
deepTools
MACS2
diffloop
R package ‘ scater ’
Biostrings
limma package
circlize
deepTools BED
GraphPad Prism

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