title: Overcoming transcription activator-like effector (TALE) DNA binding domain sensitivity to cytosine methylation.
abstract: Within the past 2 years, transcription activator-like effector (TALE) DNA binding domains have emerged as the new generation of engineerable platform for production of custom DNA binding domains. However, their recently described sensitivity to cytosine methylation represents a major bottleneck for genome engineering applications. Using a combination of biochemical, structural, and cellular approaches, we were able to identify the molecular basis of such sensitivity and propose a simple, drug-free, and universal method to overcome it.
authors.affiliation: Cellectis S.A., 8 rue de la croix Jarry, 75013 Paris, France. julien.valton@cellectis.com
authors.forename: Julien
authors.initials: J
authors.lastname: Valton
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dupuy
authors.forename: Fayza
authors.initials: F
authors.lastname: Daboussi
authors.forename: Séverine
authors.initials: S
authors.lastname: Thomas
authors.forename: Alan
authors.initials: A
authors.lastname: Maréchal
authors.forename: Rachel
authors.initials: R
authors.lastname: Macmaster
authors.forename: Kevin
authors.initials: K
authors.lastname: Melliand
authors.forename: Alexandre
authors.initials: A
authors.lastname: Juillerat
authors.forename: Philippe
authors.initials: P
authors.lastname: Duchateau
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human; D003596:Cytosine; D004247:DNA