Chemoselective labeling and site‐specific mapping of 5‐formylcytosine as a cellular nucleic acid modification

Dietzsch, Julia; Feineis, Doris; Höbartner, Claudia

doi:10.1002/1873-3468.13058

Cited by 23 publications

(25 citation statements)

References 112 publications

(233 reference statements)

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“…Using a TALE containing a p ‐acetylphenylalanine noncanonical amino acid (ncAA) incorporated by genetic code expansion (discussed in detail below), the formyl moiety of the 5fC will cross‐link to the ncAA, enabling 5fC detection [39] . The 5fC modification can also be detected by specific chemical modification to the formyl moiety [40] . Further, TALEs have also been used in nontraditional fashions.…”

Section: Dna Modificationsmentioning

confidence: 99%

Advances and Opportunities in Epigenetic Chemical Biology

2020

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The study of epigenetics has greatly benefited from the development and application of various chemical biology approaches. In this review, we highlight the key targets for modulation and recent methods developed to enact such modulation. We discuss various chemical biology techniques to study DNA methylation and the post-translational modification of histones as well as their effect on gene expression. Additionally , we address the wealth of protein synthesis approaches to yield histones and nucleosomes bearing epigenetic modifications. Throughout, we highlight targets that present opportunities for the chemical biology community, as well as exciting new approaches that will provide additional insight into the roles of epigenetic marks.

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Section: Dna Modificationsmentioning

confidence: 99%

Advances and Opportunities in Epigenetic Chemical Biology

2020

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“…A detailed account is given in a recent review by Dietzsch et al [42]. A challenge for these approaches is that abasic sites and 5-formyluracil (5fU) also display respective aldehyde groups.…”

Section: Covalent Labelingmentioning

confidence: 99%

“…The chemical reactivity of the aldehyde group in 5fC enables a plethora of covalent labeling strategies. A detailed account is given in a recent review by Dietzsch et al [42]. A challenge for these approaches is that abasic sites and 5-formyluracil (5fU) also display respective aldehyde groups.…”

Section: Covalent Labelingmentioning

confidence: 99%

Analytical epigenetics: single-molecule optical detection of DNA and histone modifications

Heck

Michaeli

Bald

et al. 2019

Current Opinion in Biotechnology

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The field of epigenetics describes the relationship between genotype and phenotype, by regulating gene expression without changing the canonical base sequence of DNA. It deals with molecular genomic information that is encoded by a rich repertoire of chemical modifications and molecular interactions. This regulation involves DNA, RNA and proteins that are enzymatically tagged with small molecular groups that alter their physical and chemical properties. It is now clear that epigenetic alterations are involved in development and disease, and thus, are the focus of intensive research. The ability to record epigenetic changes and quantify them in rare medical samples is critical for next generation diagnostics. Optical detection offers the ultimate single-molecule sensitivity and the potential for spectral multiplexing. Here we review recent progress in ultrasensitive optical detection of DNA and histone modifications.

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“…[2][3][4][5][6] Among these nucleobases, 5fC stands out by the presence of an electrophilic aldehyde group that is available for addition and condensation reactions. [7][8] Indeed, besides exhibiting unique protein interactions [9][10][11] and influencing DNA flexibility and nucleosome stability, 12 5fC can form imine-crosslinks with lysine-containing nuclear proteins and is involved in nucleosome organization. [13][14][15] Analysis of 5fC in user-defined DNA sequences is key to further unravel its biological functions.…”

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confidence: 99%

Programmable Protein–DNA Cross-Linking for the Direct Capture and Quantification of 5-Formylcytosine

et al. 2019

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5-Formylcytosine (5fC) is an epigenetic nucleobase of mammalian genomes that occurs as intermediate of active DNA demethylation. 5fC uniquely interacts and reacts with key nuclear proteins, indicating functions in genome regulation. Transcription-activatorlike effectors (TALEs) are repeat-based DNA binding proteins that can serve as probes for the direct, programmable recognition and analysis of epigenetic nucleobases. However, no TALE repeats for the selective recognition of 5fC are available, and the typically low genomic levels of 5fC represent a particular sensitivity challenge. We here advance TALE-based nucleobase targeting from recognition to covalent cross-linking. We report TALE repeats bearing the ketone-amino acid pacetylphenylalanine (pAcF) that universally bind all mammalian cytosine nucleobases, but selectively form diaminooxy-linker-mediated dioxime cross-links to 5fC. We identify repeat-linker combinations enabling single CpG resolution, and demonstrate the direct quantification of 5fC levels in a human genome background by covalent enrichment. This strategy provides a new avenue to expand the application scope of programmable probes with selectivity beyond A, G, T and C for epigenetic studies.

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Chemoselective labeling and site‐specific mapping of 5‐formylcytosine as a cellular nucleic acid modification

Cited by 23 publications

References 112 publications

Advances and Opportunities in Epigenetic Chemical Biology

Advances and Opportunities in Epigenetic Chemical Biology

Analytical epigenetics: single-molecule optical detection of DNA and histone modifications

Programmable Protein–DNA Cross-Linking for the Direct Capture and Quantification of 5-Formylcytosine

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