Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins

Nature Biotechnology

Volumn 31, Issue 12, 2013, Pages 1137-1142

  Maeder, Morgan L ^a,b   Angstman, James F ^a,c   Richardson, Marcy E ^d   Linder, Samantha J ^a   Cascio, Vincent M ^a   Tsai, Shengdar Q ^a,b   Ho, Quan H ^a   Sander, Jeffry D ^a,b   Reyon, Deepak ^a,b   Bernstein, Bradley E ^a,b,e,f   Costello, Joseph F ^g   Wilkinson, Miles F ^d   Joung, J Keith ^a,b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c HARVARD UNIVERSITY   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^f BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYTIC DOMAINS; DEMETHYLATION; DNA DEMETHYLATION; DNA METHYLATION; ENDOGENOUS GENES; FUSION PROTEINS; POTENTIAL UTILITY; THERAPEUTIC APPLICATION;

ALKYLATION; CHEMICAL ACTIVATION; GENE THERAPY; METHYLATION;

TRANSCRIPTION;

DNA; HYBRID PROTEIN; KRUPPEL LIKE FACTOR 4; OXYGENASE; PROTEIN; REAGENT; TET1 HYDROXYLASE; TRANSCRIPTION ACTIVATOR LIKE EFFECTOR PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CELL STRAIN HEK293; CONTROLLED STUDY; CPG ISLAND; DEMETHYLATION; DNA METHYLATION; EMBRYO; ENZYME ACTIVE SITE; FEMALE; GENE; GENE ACTIVATION; GENE EXPRESSION; GENE LOCUS; HBB GENE; HELA CELL; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; KRUPPEL LIKE FACTOR 4 GENE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROMOTER REGION; RHOXF2 GENE;

DNA METHYLATION; DNA-BINDING PROTEINS; GENE TARGETING; HUMANS; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS; RECOMBINANT FUSION PROTEINS; TRANSCRIPTION FACTORS; UP-REGULATION;

EID: 84890048526     PISSN: 10870156     EISSN: 15461696     Source Type: Journal    
DOI: 10.1038/nbt.2726     Document Type: Article

References (32)

1. Jones, P.A. Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484-492 (2012
2. S mith, Z.D. & Meissner, A. DNA methylation: Roles in mammalian development. Nat. Rev. Genet. 14, 204-220 (2013
3. Brena, R.M. & Costello, J.F. Genome-epigenome interactions in cancer. Hum. Mol. Genet. 16 Spec No 1, R96-R105 (2007
4. Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21 (2002
5. S uzuki, M.M. & Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet. 9, 465-476 (2008
6. R eik, W., Dean, W. & Walter, J. Epigenetic reprogramming in mammalian development. Science 293, 1089-1093 (2001
7. T ahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930-935 (2009
8. Guo, J.U., Su, Y., Zhong, C., Ming, G-L. & Song, H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145, 423-434 (2011
9. Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300-1303 (2011
10. He, Y.F. et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333, 1303-1307 (2011
11. Xu, Y. et al. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol. Cell 42, 451-464 (2011
12. Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343-348 (2011
13. Ito, S. et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129-1133 (2010
14. Joung, J.K. & Sander, J.D. TALENs: A widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 14, 49-55 (2013
15. Song, H.W. et al. The RHOX homeobox gene cluster is selectively expressed in human oocytes and male germ cells. Hum. Reprod. 28, 1635-1646 (2013
16. Mabaera, R. et al. Developmental- and differentiation-specific patterns of human gamma- and beta-globin promoter DNA methylation. Blood 110, 1343-1352 (2007
17. Maiti, A. & Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: Potential implications for active demethylation of CpG sites. J. Biol. Chem. 286, 35334-35338 (2011
18. Miller, J.C. et al. A TALE nuclease architecture for efficient genome editing. Nat. Biotechnol. 29, 143-148 (2011
19. Tan, S. et al. Zinc-finger protein-Targeted gene regulation: Genomewide single-gene specificity. Proc. Natl. Acad. Sci. USA 100, 11997-12002 (2003
20. Mendenhall, E.M. et al. Locus-specific editing of histone modifications at endogenous enhancers. Nat. Biotechnol. doi:10.1038/nbt.2701 (8 September 2013
21. Konermann, S. et al. Optical control of mammalian endogenous transcription and epigenetic states. Nature 500, 472-476 (2013
22. S nowden, A.W., Gregory, P.D., Case, C.C. & Pabo, C.O. Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr. Biol. 12, 2159-2166 (2002
23. Xu, G.L. & Bestor, T.H. Cytosine methylation targetted to pre-determined sequences. Nat. Genet. 17, 376-378 (1997
24. McNamara, A.R., Hurd, P.J., Smith, A.E.F. & Ford, K.G. Characterisation of site-biased DNA methyltransferases: Specificity, affinity and subsite relationships. Nucleic Acids Res. 30, 3818-3830 (2002
25. Carvin, C.D., Parr, R.D. & Kladde, M.P. Site-selective in vivo targeting of cytosine-5 DNA methylation by zinc-finger proteins. Nucleic Acids Res. 31, 6493-6501 (2003
26. S mith, A.E. & Ford, K.G. Specific targeting of cytosine methylation to DNA sequences in vivo. Nucleic Acids Res. 35, 740-754 (2007
27. Nomura, W. & Barbas, C.F. In vivo site-specific DNA methylation with a designed sequence-enabled DNA methylase. J. Am. Chem. Soc. 129, 8676-8677 (2007
28. Li, F. et al. Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes. Nucleic Acids Res. 35, 100-112 (2007
29. Rivenbark, A.G. et al. Epigenetic reprogramming of cancer cells via targeted DNA methylation. Epigenetics 7, 350-360 (2012
30. Siddique, A.N. et al. Targeted methylation and gene silencing of VEGF-A in human cells by using a designed Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity. J. Mol. Biol. 425, 479-491 (2013
31. Reyon, D. et al. FLASH assembly of TALENs for high-Throughput genome editing. Nat. Biotechnol. 30, 460-465 (2012
32. Maeder, M.L. et al. Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol. Cell 31, 294-301 (2008