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Konstantin Lephikov

Bio: Konstantin Lephikov is an academic researcher from Saarland University. The author has contributed to research in topics: DNA repair & DNA damage. The author has an hindex of 1, co-authored 1 publications receiving 832 citations.

Papers
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Journal ArticleDOI
28 Feb 2013-Cell
TL;DR: Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation.

897 citations


Cited by
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Journal ArticleDOI
15 Jan 2015-Nature
TL;DR: These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation, which is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker.
Abstract: Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout.

1,564 citations

Journal ArticleDOI
24 Oct 2013-Nature
TL;DR: Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.
Abstract: DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.

1,336 citations

Journal ArticleDOI
TL;DR: The mechanisms and functions of DNA methylation and demethylation in both mice and humans at CpG-rich promoters, gene bodies and transposable elements are discussed and the dynamic erasure and re-establishment in embryonic, germline and somatic cell development is highlighted.
Abstract: DNA methylation is of paramount importance for mammalian embryonic development. DNA methylation has numerous functions: it is implicated in the repression of transposons and genes, but is also associated with actively transcribed gene bodies and, in some cases, with gene activation per se. In recent years, sensitive technologies have been developed that allow the interrogation of DNA methylation patterns from a small number of cells. The use of these technologies has greatly improved our knowledge of DNA methylation dynamics and heterogeneity in embryos and in specific tissues. Combined with genetic analyses, it is increasingly apparent that regulation of DNA methylation erasure and (re-)establishment varies considerably between different developmental stages. In this Review, we discuss the mechanisms and functions of DNA methylation and demethylation in both mice and humans at CpG-rich promoters, gene bodies and transposable elements. We highlight the dynamic erasure and re-establishment of DNA methylation in embryonic, germline and somatic cell development. Finally, we provide insights into DNA methylation gained from studying genetic diseases. DNA methylation is essential for mammalian embryogenesis owing to its repression of transposons and genes, but it is also associated with gene activation. The recent use of sensitive technologies has revealed that DNA methylation dynamics vary considerably between embryonic, germline and somatic cell development, with implications for genetic diseases and cancer.

1,039 citations

Journal ArticleDOI
TL;DR: Recent advances in biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation and many regulatory mechanisms of this process have been identified.
Abstract: A key mode of regulating DNA methylation is through active demethylation driven by TET-mediated oxidation of 5-methylcytosine (5mC). This Review discusses our latest understanding of the mechanisms and regulation of active DNA demethylation, and the roles of active demethylation (and the oxidized 5mC intermediates) in gene regulation, genome stability, development and disease.

1,012 citations

Journal ArticleDOI
TL;DR: Although CTCF has been assigned various roles that are often contradictory, new results now help to draw a unifying model to explain the many functions of this protein.
Abstract: CCCTC-binding factor (CTCF) is a DNA-binding protein that has various, often seemingly contradictory, roles in gene regulation. This Review describes these disparate functions and how the context-dependent looping of DNA regions by CTCF is emerging as a potential unifying mechanism that underpins these diverse roles.

930 citations