skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD

Authors:
 [1];  [2];  [3];  [1];  [4];  [1];  [3];  [1]
  1. Neuromuscular Research Group Department of Neurology University Hospital Basel Basel Switzerland, Neuromuscular Research Group Department of Biomedicine University Hospital Basel Basel Switzerland
  2. Neuromuscular Research Group Department of Neurology University Hospital Basel Basel Switzerland, Neuromuscular Research Group Department of Biomedicine University Hospital Basel Basel Switzerland, Department of Health Technology Technical University of Denmark Kgs Lyngby Denmark
  3. Department of Biochemistry, Molecular Biology, and Biophysics University of Minnesota Minneapolis MN USA
  4. Lillehei Heart Institute University of Minnesota Minneapolis MN USA, Department of Pediatrics University of Minnesota Minneapolis MN USA
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1597528
Alternate Identifier(s):
OSTI ID: 1597529
Grant/Contract Number:  
DE‐AC02‐06CH11357
Resource Type:
Published Article
Journal Name:
FASEB Journal
Additional Journal Information:
Journal Name: FASEB Journal; Journal ID: ISSN 0892-6638
Publisher:
FASEB
Country of Publication:
United States
Language:
English

Citation Formats

Klingler, Christian, Ashley, Jon, Shi, Ke, Stiefvater, Adeline, Kyba, Michael, Sinnreich, Michael, Aihara, Hideki, and Kinter, Jochen. DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD. United States: N. p., 2020. Web. doi:10.1096/fj.201902696.
Klingler, Christian, Ashley, Jon, Shi, Ke, Stiefvater, Adeline, Kyba, Michael, Sinnreich, Michael, Aihara, Hideki, & Kinter, Jochen. DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD. United States. doi:10.1096/fj.201902696.
Klingler, Christian, Ashley, Jon, Shi, Ke, Stiefvater, Adeline, Kyba, Michael, Sinnreich, Michael, Aihara, Hideki, and Kinter, Jochen. Wed . "DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD". United States. doi:10.1096/fj.201902696.
@article{osti_1597528,
title = {DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD},
author = {Klingler, Christian and Ashley, Jon and Shi, Ke and Stiefvater, Adeline and Kyba, Michael and Sinnreich, Michael and Aihara, Hideki and Kinter, Jochen},
abstractNote = {},
doi = {10.1096/fj.201902696},
journal = {FASEB Journal},
number = ,
volume = ,
place = {United States},
year = {2020},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1096/fj.201902696

Save / Share:

Works referenced in this record:

Solution structure of dAATAA and dAAUAA DNA bulges
journal, June 2002


Structural basis for multiple gene regulation by human DUX4
journal, November 2018

  • Li, Yangyang; Wu, Baixing; Liu, Hehua
  • Biochemical and Biophysical Research Communications, Vol. 505, Issue 4
  • DOI: 10.1016/j.bbrc.2018.10.056

JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles
journal, November 2013

  • Mathelier, Anthony; Zhao, Xiaobei; Zhang, Allen W.
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt997

Analysis of the Binding of p53 to DNAs Containing Mismatched and Bulged Bases
journal, December 2000

  • Degtyareva, Natalya; Subramanian, Deepa; Griffith, Jack D.
  • Journal of Biological Chemistry, Vol. 276, Issue 12
  • DOI: 10.1074/jbc.M006795200

The multifaceted mismatch-repair system
journal, April 2006

  • Jiricny, Josef
  • Nature Reviews Molecular Cell Biology, Vol. 7, Issue 5
  • DOI: 10.1038/nrm1907

Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons
journal, May 2017

  • Hendrickson, Peter G.; Doráis, Jessie A.; Grow, Edward J.
  • Nature Genetics, Vol. 49, Issue 6
  • DOI: 10.1038/ng.3844

CRISPR/dCas9-mediated Transcriptional Inhibition Ameliorates the Epigenetic Dysregulation at D4Z4 and Represses DUX4-fl in FSH Muscular Dystrophy
journal, March 2016

  • Himeda, Charis L.; Jones, Takako I.; Jones, Peter L.
  • Molecular Therapy, Vol. 24, Issue 3
  • DOI: 10.1038/mt.2015.200

New oncogenic subtypes in pediatric B-cell precursor acute lymphoblastic leukemia
journal, September 2017


Pax7 is critical for the normal function of satellite cells in adult skeletal muscle
journal, September 2013

  • von Maltzahn, J.; Jones, A. E.; Parks, R. J.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 41
  • DOI: 10.1073/pnas.1307680110

A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death
journal, September 2019

  • Bosnakovski, Darko; da Silva, Meiricris T.; Sunny, Sithara T.
  • Science Advances, Vol. 5, Issue 9
  • DOI: 10.1126/sciadv.aaw7781

In vitro selection of RNA molecules that bind specific ligands
journal, August 1990

  • Ellington, Andrew D.; Szostak, Jack W.
  • Nature, Vol. 346, Issue 6287
  • DOI: 10.1038/346818a0

Exceptionally Stable Nucleic Acid Hairpins
journal, June 1995


Analysis of protein-ligand interactions by fluorescence polarization
journal, March 2011


Solution Structure of a Five-Adenine Bulge Loop within a DNA Duplex
journal, September 1999

  • Dornberger, Utz; Hillisch, Alexander; Gollmick, Friedrich A.
  • Biochemistry, Vol. 38, Issue 39
  • DOI: 10.1021/bi9906874

Mutations in DNMT3B Modify Epigenetic Repression of the D4Z4 Repeat and the Penetrance of Facioscapulohumeral Dystrophy
journal, May 2016

  • van den Boogaard, Marlinde L.; Lemmers, Richard J. L. F.; Balog, Judit
  • The American Journal of Human Genetics, Vol. 98, Issue 5
  • DOI: 10.1016/j.ajhg.2016.03.013

XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/S0907444909047337

AptaSUITE: A Full-Featured Bioinformatics Framework for the Comprehensive Analysis of Aptamers from HT-SELEX Experiments
journal, June 2018


Genome-Wide Analysis of RNA Secondary Structure
journal, November 2016


Increase in nuclease resistance and incorporation of NF-κB decoy oligodeoxynucleotides by modification of the 3′-terminus
journal, January 2007

  • Osako, Mariana Kiomy; Tomita, Naruya; Nakagami, Hironori
  • The Journal of Gene Medicine, Vol. 9, Issue 9
  • DOI: 10.1002/jgm.1077

Transcription factor decoy technology: A therapeutic update
journal, November 2017


What's in a name? The clinical features of facioscapulohumeral muscular dystrophy
journal, February 2016


Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis
journal, May 2006

  • Strong, M.; Sawaya, M. R.; Wang, S.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 21
  • DOI: 10.1073/pnas.0602606103

Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics
journal, August 2016

  • Chen, Jennifer CJ; King, Oliver D.; Zhang, Yuanfan
  • Molecular Therapy, Vol. 24, Issue 8
  • DOI: 10.1038/mt.2016.111

Efficient Recognition of an Unpaired Lesion by a DNA Repair Glycosylase
journal, December 2009

  • Lyons, Derek M.; O’Brien, Patrick J.
  • Journal of the American Chemical Society, Vol. 131, Issue 49
  • DOI: 10.1021/ja908378y

Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery
journal, January 2019

  • Correa, Fernanda A.; Nakaguma, Marilena; Madeira, João L. O.
  • Archives of Endocrinology and Metabolism, Vol. 63, Issue 2
  • DOI: 10.20945/2359-3997000000139

Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo
journal, June 2016

  • Yoon, Sorah; Huang, Kai-Wen; Reebye, Vikash
  • Molecular Therapy, Vol. 24, Issue 6
  • DOI: 10.1038/mt.2016.60

Therapeutic applications of synthetic nucleic acid aptamers
journal, December 2017


Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2
journal, November 2012

  • Lemmers, Richard J. L. F.; Tawil, Rabi; Petek, Lisa M.
  • Nature Genetics, Vol. 44, Issue 12
  • DOI: 10.1038/ng.2454

Characterizing the bending and flexibility induced by bulges in DNA duplexes
journal, April 2015

  • Schreck, John S.; Ouldridge, Thomas E.; Romano, Flavio
  • The Journal of Chemical Physics, Vol. 142, Issue 16
  • DOI: 10.1063/1.4917199

Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA
journal, December 2018


DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade
journal, September 2019


DNA-binding sequence specificity of DUX4
journal, December 2015


The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein
journal, August 2007

  • Kowaljow, Valeria; Marcowycz, Aline; Ansseau, Eugénie
  • Neuromuscular Disorders, Vol. 17, Issue 8
  • DOI: 10.1016/j.nmd.2007.04.002

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

DUX4c, an FSHD candidate gene, interferes with myogenic regulators and abolishes myoblast differentiation
journal, November 2008


The FSHD Atrophic Myotube Phenotype Is Caused by DUX4 Expression
journal, October 2011


Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults
journal, March 2016

  • Yasuda, Takahiko; Tsuzuki, Shinobu; Kawazu, Masahito
  • Nature Genetics, Vol. 48, Issue 5
  • DOI: 10.1038/ng.3535

Therapeutic modulators of STAT signalling for human diseases
journal, August 2013

  • Miklossy, Gabriella; Hilliard, Tyvette S.; Turkson, James
  • Nature Reviews Drug Discovery, Vol. 12, Issue 8
  • DOI: 10.1038/nrd4088

Aptamers in the Therapeutics and Diagnostics Pipelines
journal, January 2018

  • Kaur, Harleen; Bruno, John G.; Kumar, Amit
  • Theranostics, Vol. 8, Issue 15
  • DOI: 10.7150/thno.25958

Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease
journal, February 2006

  • Ng, Eugene W. M.; Shima, David T.; Calias, Perry
  • Nature Reviews Drug Discovery, Vol. 5, Issue 2
  • DOI: 10.1038/nrd1955

First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy
journal, June 2012


Expression of DUX4 in zebrafish development recapitulates facioscapulohumeral muscular dystrophy
journal, October 2012

  • Mitsuhashi, Hiroaki; Mitsuhashi, Satomi; Lynn-Jones, Taylor
  • Human Molecular Genetics, Vol. 22, Issue 3
  • DOI: 10.1093/hmg/dds467

Dimeric PROP1 binding to diverse palindromic TAAT sequences promotes its transcriptional activity
journal, August 2009

  • Nakayama, Michie; Kato, Takako; Susa, Takao
  • Molecular and Cellular Endocrinology, Vol. 307, Issue 1-2
  • DOI: 10.1016/j.mce.2009.03.010

Influence of Repressive Histone and DNA Methylation upon D4Z4 Transcription in Non-Myogenic Cells
journal, July 2016


DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1
journal, November 2007

  • Dixit, M.; Ansseau, E.; Tassin, A.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 46
  • DOI: 10.1073/pnas.0708659104

A family history of DUX4: phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUX gene
journal, January 2010


Nucleic Acid Aptamers: An Emerging Tool for Biotechnology and Biomedical Sensing
journal, July 2015

  • Ku, Ti-Hsuan; Zhang, Tiantian; Luo, Hua
  • Sensors, Vol. 15, Issue 7
  • DOI: 10.3390/s150716281

High-throughput screening identifies inhibitors of DUX4-induced myoblast toxicity
journal, January 2014

  • Bosnakovski, Darko; Choi, Si; Strasser, Jessica M.
  • Skeletal Muscle, Vol. 4, Issue 1
  • DOI: 10.1186/2044-5040-4-4

Population-based incidence and prevalence of facioscapulohumeral dystrophy
journal, August 2014


Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia
journal, June 2016


A Mutant Sumo Facilitates Quick Plasmid Construction for Expressing Proteins with Native N-termini After Tag Removal
journal, March 2017


Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene
journal, October 2010


DUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes
journal, March 2016

  • Choi, Si Ho; Gearhart, Micah D.; Cui, Ziyou
  • Nucleic Acids Research, Vol. 44, Issue 11
  • DOI: 10.1093/nar/gkw141

The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy
journal, August 2019


PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle
journal, December 2017

  • Banerji, Christopher R. S.; Panamarova, Maryna; Hebaishi, Husam
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/s41467-017-01200-4

Management strategies in facioscapulohumeral muscular dystrophy
journal, January 2019

  • Lu, Junren; Yao, Zhenjun; Yang, Yi
  • Intractable & Rare Diseases Research, Vol. 8, Issue 1
  • DOI: 10.5582/irdr.2019.01016

Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies
journal, January 1997

  • Lee, Seong-Wook; Sullenger, Bruce A.
  • Nature Biotechnology, Vol. 15, Issue 1
  • DOI: 10.1038/nbt0197-41

RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of facioscapulohumeral dystrophy
journal, April 2009

  • Snider, Lauren; Asawachaicharn, Amy; Tyler, Ashlee E.
  • Human Molecular Genetics, Vol. 18, Issue 13
  • DOI: 10.1093/hmg/ddp180

A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy
journal, August 2010

  • Lemmers, R. J. L. F.; van der Vliet, P. J.; Klooster, R.
  • Science, Vol. 329, Issue 5999
  • DOI: 10.1126/science.1189044

Selection and Biosensor Application of Aptamers for Small Molecules
journal, June 2016


The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain
journal, September 2017

  • Bosnakovski, Darko; Toso, Erik A.; Hartweck, Lynn M.
  • Journal of Cell Science, Vol. 130, Issue 21
  • DOI: 10.1242/jcs.205427

Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade
journal, September 2017


Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation
journal, May 2006

  • Kawamura-Saito, Miho; Yamazaki, Yukari; Kaneko, Keiko
  • Human Molecular Genetics, Vol. 15, Issue 13
  • DOI: 10.1093/hmg/ddl136

Pegaptanib: In Exudative Age-Related Macular Degeneration
journal, January 2005


Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways
journal, August 2015

  • Rickard, Amanda M.; Petek, Lisa M.; Miller, Daniel G.
  • Human Molecular Genetics, Vol. 24, Issue 20
  • DOI: 10.1093/hmg/ddv315

Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen
journal, July 2016

  • Choi, Si Ho; Bosnakovski, Darko; Strasser, Jessica M.
  • Journal of Biomolecular Screening, Vol. 21, Issue 7
  • DOI: 10.1177/1087057116651868

Unravelling mechanisms of p53-mediated tumour suppression
journal, April 2014

  • Bieging, Kathryn T.; Mello, Stephano Spano; Attardi, Laura D.
  • Nature Reviews Cancer, Vol. 14, Issue 5
  • DOI: 10.1038/nrc3711

Fusion of EWSR1 with the DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma
journal, November 2009


JASPAR: an open-access database for eukaryotic transcription factor binding profiles
journal, January 2004


CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma
journal, April 2017


DUX4 Pathological Expression: Causes and Consequences in Cancer
journal, May 2019


Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: evidence for disease modifiers and a quantitative model of pathogenesis
journal, July 2012

  • Jones, Takako Iida; Chen, Jennifer C. J.; Rahimov, Fedik
  • Human Molecular Genetics, Vol. 21, Issue 20
  • DOI: 10.1093/hmg/dds284

RNA Interference Inhibits DUX4-induced Muscle Toxicity In Vivo: Implications for a Targeted FSHD Therapy
journal, July 2012

  • Wallace, Lindsay M.; Liu, Jian; Domire, Jacqueline S.
  • Molecular Therapy, Vol. 20, Issue 7
  • DOI: 10.1038/mt.2012.68

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

Functional domains of the FSHD-associated DUX4 protein
journal, April 2018

  • Mitsuhashi, Hiroaki; Ishimaru, Satoshi; Homma, Sachiko
  • Biology Open, Vol. 7, Issue 4
  • DOI: 10.1242/bio.033977

Sequence-specific inhibition of a transcription factor by circular dumbbell DNA oligonucleotides
journal, November 1999


Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development
journal, May 2019


Deregulation of DUX4 and ERG in acute lymphoblastic leukemia
journal, October 2016

  • Zhang, Jinghui; McCastlain, Kelly; Yoshihara, Hiroki
  • Nature Genetics, Vol. 48, Issue 12
  • DOI: 10.1038/ng.3691

Protein kinase A activation inhibits DUX4 gene expression in myotubes from patients with facioscapulohumeral muscular dystrophy
journal, June 2018

  • Cruz, Joseph M.; Hupper, Nicole; Wilson, Liz S.
  • Journal of Biological Chemistry, Vol. 293, Issue 30
  • DOI: 10.1074/jbc.RA118.002633

An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies
journal, October 2008

  • Bosnakovski, Darko; Xu, Zhaohui; Ji Gang, Eun
  • The EMBO Journal, Vol. 27, Issue 20
  • DOI: 10.1038/emboj.2008.201

Dose-Response Analysis Using R
journal, December 2015


Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia
journal, June 2016

  • Lilljebjörn, Henrik; Henningsson, Rasmus; Hyrenius-Wittsten, Axel
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms11790

DNAshapeR: an R/Bioconductor package for DNA shape prediction and feature encoding
journal, December 2015


DUX4 Activates Germline Genes, Retroelements, and Immune Mediators: Implications for Facioscapulohumeral Dystrophy
journal, January 2012


Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism
journal, November 1996

  • Sornson, Mark W.; Wu, Wei; Dasen, Jeremy S.
  • Nature, Vol. 384, Issue 6607
  • DOI: 10.1038/384327a0

DUX4 Binding to Retroelements Creates Promoters That Are Active in FSHD Muscle and Testis
journal, November 2013


DUX-family transcription factors regulate zygotic genome activation in placental mammals
journal, May 2017

  • De Iaco, Alberto; Planet, Evarist; Coluccio, Andrea
  • Nature Genetics, Vol. 49, Issue 6
  • DOI: 10.1038/ng.3858

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Conservative secondary structure motif of streptavidin-binding aptamers generated by different laboratories
journal, March 2010

  • Bing, Tao; Yang, Xiaojuan; Mei, Hongcheng
  • Bioorganic & Medicinal Chemistry, Vol. 18, Issue 5
  • DOI: 10.1016/j.bmc.2010.01.054