UCOE® References - Mammalian Expression

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ArticleApplicationCell TypeUCOE element usedProtein Expressed
Correlation of DNA methylation with histone modifications across the HNRPA2B1-CBX3 ubiquitously-acting chromatin open element (UCOE). Lindahl Allen M, Antoniou M. Epigenetics. 2007 Oct-Dec;2(4):227-36. Basic mechanisms Human peripheral blood mononuclear cells (PBMCs) 5kb human
HNRPA2B1-CBX3 region
Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes. Majocchi S, Aritonovska E, Mermod N. Nucleic Acids Res. 2014 Jan;42(1):193-204. Basic mechanisms HeLa 1.5kb human HNRPA2B1 N/A
Integrative analysis of methylome and transcriptome reveals the importance of unmethylated CpGs in non-CpG island gene activation. Marx A, Kahan T, Simon I. Biomed Res Int. 2013 2013:785731. Basic mechanisms N/A N/A N/A
Transcriptional Regulation of the Human TATA Binding Protein Gene. Harland L, Crombie R, Anson S, deBoer J, Ioannou PA, Antoniou M. Genomics. 2002 Apr;79(4):479-82. Basic mechanisms Murine L-cells 44 kb human TBP region N/A
Transgenes encompassing dual-promoter CpG islands from the human TBP and HNRPA2B1 loci are resistant to heterochromatin-mediated silencing. Antoniou M, Harland L, Mustoe T, Williams S, Holdstock J, Yague E, Mulcahy T, Griffiths M, Edwards S, Ioannou PA, M Basic mechanisms Murine L-cells
25 kb human TBP;
16 kb human HNRPA2B1
Interplay of Promoter Usage and Intragenic CpG Content: Impact on GFP Reporter Gene Expression. Krinner S, Heitzer A, Asbach B, Wagner R. Hum Gene Ther. 2015 Dec;26(12):826-40. doi: 10.1089/hum.2015.075. Epub 2015 Sep 29. Bioprocessing Flp-In CHO
2.2 kb human HNRPA2B1; expression from HNRPA2B1 promoter EGFP
Assessment of UCOE on Recombinant EPO Production and Expression Stability in Amplified Chinese Hamster Ovary Cells. Betts Z, Dickson AJ. Mol Biotechnol. 2015 Sep;57(9):846-58. doi: 10.1007/s12033-015-9877-y. Bioprocessing CHO-DG44 8kb human HNRPA2B1 linked upstream of hCMV promoter   EPO
Chromatin Function Modifying Elements in an Industrial Antibody Production Platform - Comparison of UCOE, MAR, STAR and cHS4 Elements. Saunders F, Sweeney B, Antoniou MN, Stephens P, Cain K. PLoS One. 2015 Apr 7;10(4):e0120096. Bioprocessing CHO-K1 1.5kb human HNRPA2B1 linked upstream of hCMV promoter mAb
CpG-island fragments from the HNRPA2B1/CBX3 genomic locus reduce silencing and enhance transgene expression from the hCMV promoter/enhancer in mammalian cells. Williams S, Mustoe T, Mulcahy T, Griffiths M, Simpson D, Antoniou M, Irvine A, Mountain A, Crom Bioprocessing CHO-K1 1.5 kb
4 kb
8 kb
human HNRPA2B1, all linked upstream of hCMV promoter
Effect of different UCOE-promoter combinations in creation of engineered cell lines for the production of Factor VIII. Nair AR, Jinger X, Hermiston TW. BMC Res Notes. 2011 Jun 10;4:178. Bioprocessing BHK21 1.5 kb human HNRPA2B1;
3.2 kb mouse Rps3; linked upstream of hCMV
B domain deleted factor VIII (BDD-FVIII)
Evaluating the interaction between UCOE and DHFR-linked amplification and stability of recombinant protein expression. Betts Z, Croxford AS, Dickson AJ. Biotechnol Prog. 2015 Jul-Aug;31(4):1014-25. doi: 10.1002/btpr.2083. Epub 2015 Apr 8. Bioprocessing CHO-DG44 8 kb human HNRPA2B1 upstream of hCMV EGFP
High-throughput ClonePix FL analysis of mAb-expressing clones using the UCOE expression system. Hou JJ, Hughes BS, Smede M, Leung KM, Levine K, Rigby S, Gray PP, Munro TP. N Biotechnol. 2014 May 25;31(3):214-20. Bioprocessing CHO-K1 (CHO XL-99) 3.2 kb mouse Rps3,
8 kb human HNRPA2B1; linked upstream of gpCMV & hCMV
Rapid protein production using CHO stable transfection pools. Ye J, Alvin K, Latif H, Hsu A, Parikh V, Whitmer T, Tellers M, de la Cruz Edmonds MC, Ly J, Salmon P, Markusen JF. Biotechnol Prog. 2010 Sep-Oct;26(5):1431-7. Bioprocessing CHO-K1SV 3.2 kb mouse Rps3, linked upstream of hCMV Model Abs
Simple scale-up of recombinant antibody production using an UCOE containing vector. Boscolo S, Mion F, Licciulli M, Macor P, De Maso L, Brce M, Antoniou MN, Marzari R, Santoro C, Sblattero D. N Biotechnol. 2012 May 15;29(4):477-84. Bioprocessing CHO-S 4 kb human HNRPA2B1, linked upstream of hCMV Dipeptil peptidase 6 - DPP6 (human)
Transglutaminase 2 - TG2 (human)
TRAIL R2 (human)
Complement 5
Stable expression of H1C2 monoclonal antibody in NS0 and CHO cells using pFUSE and UCOE expression system. Dharshanan S, Chong H, Cheah SH, Zamrod Z. Cytotechnology. 2013 Jul 24. Bioprocessing NS0
3.2 kb mouse Rps3, linked upstream of hCMV humanized anti-C2 (H1C2 mAb)
The use of UCOE vectors in combination with a preadapted serum free, suspension cell line allows for rapid production of large quantities of protein. Benton T, Chen T, McEntee M, Fox B, King D, Crombie R, Thomas TC, Bebbington C. Cytotechnology. 2002 Jan; Bioprocessing CHO-K1
8kb human HNRPA2B1, linked upsteam of hCMV GFP
humanized mAb
Ubiquitous Chromatin Opening Elements (UCOEs) effect on transgene position and expression stability in CHO cells following methotrexate (MTX) amplification. Betts Z and Dickson AJ. Biotechnol J. 2015 Dec 3. doi: 10.1002/biot.201500159. [Epub ahead of prin Bioprocessing CHO-DG44 8 kb human HNRPA2B1, linked upstream of hCMV EGFP
Daedalus: a robust, turnkey platform for rapid production of decigram quantities of active recombinant proteins in human cell lines using novel lentiviral vectors. Bandaranayake AD1, Correnti C, Ryu BY, Brault M, Strong RK, Rawlings DJ. Nucleic Acids Res. Bioprocessing 293 Freestyle; CHO-S 2kb human,
0.7 kb human HNRPA2B1; linked upstream of SFFV
Siderocalin (human & mouse)
Lipocalin 15 (human)
Glycodelin (human)
MICA (soluble)
MICA alpha 3
IL-3 (canine)
G-CSF (canine)
IL-7 (human)
LIF (human); EGFP
A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors. Zhang F, Frost AR, Blundell MP, Bales O, Antoniou MN, Thrasher AJ. Mol Ther. 2010 Sep;18(9):1640-9. Lentivirus Murine P19 embryonal carcinoma
Murine HSC
2.2kb human HNRPA2B1; expression from HNRPA2B1 promoter; 1.5/1.2kb human HNRPA2B1 linked upstream of SFFV promoter  EGFP
Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene. van Til NP, de Boer H, Mashamba N, Wabik A, Huston M, Visser TP, Fontana E, Poliani PL, Cassani B, Zhang F, Thrasher  Lentivirus Murine HSC targetted; Rag2 KO mice; effects measured in peripheral blood mononuclear cells 2.2kb human HNRPA2B1; expression from HNRPA2B1 promoter  Rag2 protein
Lentiviral MGMT(P140K)-mediated in vivo selection employing a ubiquitous chromatin opening element (A2UCOE) linked to a cellular promoter. Phaltane R, Lachmann N, Brennig S, Ackermann M, Modlich U, Moritz T. Biomaterials. 2014 Aug;35(25):7204-13. Lentivirus Murine HSC; effects measured in peripheral blood cells 1.5kb human HNRPA2B1, linked upstream of murine PGK promoter MGMT, EGFP
Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells. Zhang F, Thornhill SI, Howe SJ, Ulaganathan M, Schambach A, Sinclair J, Lentivirus K562
ED-7R                                         Murine HSC
2.2 kb human HNRPA2B1; expression from HNRPA2B1 promoter EGFP
Long-Term Reproducible Expression in Human Fetal Liver Hematopoietic Stem Cells with a UCOE-Based Lentiviral Vector. Dighe N, Khoury M, Mattar C, Chong M, Choolani M, Chen J, Antoniou MN, Chan JK. PLoS One. 2014 Aug 12;9(8). Lentivirus Human fetal liver-derived HSC (hflHSC) 2.2 kb human HNRPA2B1; expression from HNRPA2B1 promoter EGFP
Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter. Brendel C, Müller-Kuller U, Schultze-Strasser S, Stein S, Chen-Wichmann L, Krattenmacher A, Kunkel H, Dillmann A, Antoniou MN, Grez Lentivirus PLB985, PLB985 gp91phox-/-
HUT-78; murine HSC
1.5kb human HNRPA2B1, linked upstream of MRP8 promoter  gp91phox
The human desmin promoter drives robust gene expression for skeletal muscle stem cell-mediated gene therapy. Jonuschies J, Antoniou M, Waddington S, Boldrin L, Muntoni F, Thrasher A, Morgan J. Curr Gene Ther. 2014 14(4):276-288. Lentivirus Murine C2C12 myoblasts; H-2Kb-tsA58-Myf5nLacZ/+ conditionally immortalised murine myoblasts; primary murine skeletal muscle satellite cells; human immortalised myoblasts   2.2kb human HNRPA2B1; expression from HNRPA2B1 promoter; 1.5kb  human HNRPA2B1 linked upstream of human Desmin promoter  GFP
A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells. Müller-Kuller U, Ackermann M, Kolodziej S, Brendel C, Fritsch J,  Lentivirus P19
Mouse Lin- HSC
hCD34iPSC11 (iPSC)
Jurkat cells
1.5 kb/674bp human HNRPA2B1 linked upstream of SFFV & MRP8; 674 bp  human CBX3; expression from CBX3 promoter EGFP
A ubiquitous chromatin opening element prevents transgene silencing in pluripotent stem cells and their differentiated progeny. Pfaff N, Lachmann N, Ackermann M, Kohlscheen S, Brendel C, Maetzig T, Niemann H, Antoniou MN, Grez M, Schambach A, Cantz T, Mor Lentivirus Murine iPSC-7
Human hES3
1.5 kb human HNRPA2B1, linked upstream of SFFV, EF1a Human cytidine daminase (CDD) dTomato
Biphasic modulation of Wnt signalling supports efficient foregut endoderm formation from human pluripotent stem cells. Hoepfner J, Kleinsorge M, Papp O, Ackermann M, Alfken S, Rinas U, Solodenko W, Kirschning A, Sgodda M, Cantz T. Cell Biol Int. 2016 Feb  Lentivirus H9 human ES cells
hFLF-4 human iPS cells
MEF primary murine embryonic fibroblasts
1.5 kb human HNRPA2B1, upstream of EF1a, TCF4/LEF1 dTomato
Firefly luciferase
Promoter and lineage independent anti-silencing activity of the A2 ubiquitous chromatin opening element for optimized human pluripotent stem cell-based gene therapy. Ackermann M, Lachmann N, Hartung S, Eggenschwiler R, Pfaff N, Happle C, Mucci A, Göhring  Lentivirus miPSC line lin-7
hCD34-derived iPS cells
H9 human ES cells
1.5 kb human HNRPA2B1, upstream of EF1a, SFFV dTomato
human cytidine daminase (CDD)
Desmin-regulated Lentiviral Vectors for Skeletal Muscle Gene Transfer. Talbot GE, Waddington SN, Bales O, Tchen RC, Antoniou MN. Mol Ther. 2010 Mar;18(3):601-8. Lentivirus L cells, murine fibroblasts;
C2C12, murine myoblasts
MF1 mouse skeletal muscle 
1.5 kb human HNRPA2B1, upstream of human Desmin promoter EGFP
Lentiviral vector transduction of spermatozoa as a tool for the study of early development. Chandrashekran A, Isa I, Dudhia J, Thrasher AJ, Dibb N, Casimir C, Readhead C, Winston R. FEBS Open Bio. 2014 Mar 3;4:266-75. Lentivirus Boar spermatozoa
B6/CBA1 mouse sperm
2.5 kb human HNRPA2B1; expression from HNRPA2B1 promoter EGFP
Safer, Silencing-Resistant Lentiviral Vectors: Optimization of the Ubiquitous Chromatin-Opening Element through Elimination of Aberrant Splicing. Knight S, Zhang F, Mueller-Kuller U, Bokhoven M, Gupta A, Broughton T, Sha S, Antoniou MN, Brendel C, Grez M, Lentivirus Bcl-15, murine B-cell lymphoma;
PLB-985, human myelomonocytic cells;
2.2 kb human HNRPA2B1; expression from HNRPA2B1 promoter; 1.5 kb human HNRPA2B1, upstream of PGK, MRP8 promoters IL-2RG
Foamy virus vector-mediated gene correction of a mouse model of Wiskott-Aldrich syndrome. Uchiyama T, Adriani M, Jagadeesh GJ, Paine A, Candotti F. Mol Ther. 2012 Jun;20(6):1270-9. Other vectors Murine HSC; WAS KO mice; effects measured in peripheral blood mononuclear cells 631 bp human HNRPA2B1; expression from HNRPA2B1 promoter WAS protein
Optimization of short-term transgene expression by sodium butyrate and ubiquitous chromatin opening elements (UCOEs). de Poorter JJ, Lipinski KS, Nelissen RG, Huizinga TW, Hoeben RC. J Gene Med. 2007 Aug;9(8):639-48. Other vectors Diploid human interface cells 1.5kb human HNRPA2B1, linked upstream of hCMV Luciferase
Gene Expression Profile and Toxic Effects in Human Bronchial Epithelial Cells Exposed to Zearalenone. So MY, Tian Z, Phoon YS, Sha S, Antoniou MN, Zhang JW, Wu RS, Tan-Un KC. PLoS One. 2014  May 2;9(5). Other vectors BEAS-2B (human bronchial epithelial cells) 1.5 kb human HNRPA2B1, linked upstream of hCMV Cytoglobin (Cygb)
Genomic cis-acting Sequences Improve Expression and Establishment of a Nonviral Vector. Hagedorn C, Antoniou MN, Lipps HJ. Mol Ther Nucleic Acids. 2013 Sep 3;2:e118. Other vectors CHO 1.5 kb human HNRPA2B1, linked upstream of hCMV EGFP
Ubiquitous expression of the rtTA2S-M2 inducible system in transgenic mice driven by the human hnRNPA2B1/CBX3 CpG island. Katsantoni EZ, Anghelescu NE, Rottier R, Moerland M, Antoniou M, de Crom R, Grosveld F, Strouboulis J. BMC Dev Biol. 2007 Sep 27;7:10 Other vectors Transgenic mice 8 kb human HNRPA2B1; expression from HNRPA2B1 promoter Dox inducible rtTA2S-M2 Tet-transactivator
Optimizing retroviral gene expression for effective therapies. Antoniou MN, Skipper KA, Anakok O. Hum Gene Ther. 2013 Apr;24(4):363-74. Review N/A N/A N/A
Regulatory Elements in Vectors for Efficient Generation of Cell Lines Producing Target Proteins. Maksimenko O, Gasanov NB, Georgiev P. Acta Naturae. 2015 Jul-Sep;7(3):15-26. Review N/A N/A N/A