DNA Demethylation, DNA Repair and Reprogramming
Some 70 years after Watson & Crick, our understanding of the mechanisms whereby DNA relates genetic information is still incomplete. For example, the recent discovery of three modified bases in mammalian DNA, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), was wholly surprising, and we still do not know if these bases are primarily DNA demethylation intermediates or whether they have epigenetic roles in their own right. Our lab conducts epigenetic research with modified nucleobases at the interface of development and ageing.
One main aim of research in the Niehrs group is to understand the mechanisms of DNA demethylation as well as the biological roles of 5hmC, 5fC, and 5caC during development. In this context, we characterise the small stress response and demethylation protein Gadd45. We focus on locus-specificity of demethylation, as well as the role of Gadd45 in development and differentiation. We also analyze other modified nucleobases, including N6-methyl-deoxyadenosine and DNA poly-(ADP)ribosylation, and characterise their potential epigenetic role and relevant effectors in this context.
We utilise biochemical, omics-, and cell biological approaches, and employ mouse and Xenopus embryos and mouse embryonic stem cells (ESCs) as developmental model systems. Finally, we investigate demethylation in the context of cellular and organismic ageing, where DNA methylation and epigenetic changes are a hallmark.
- Since 2020: Executive Director, Institute of Molecular Biology (IMB), Mainz
- Since 2010: Founding & Scientific Director, Institute of Molecular Biology (IMB), Mainz; Professor, Faculty of Biology, Johannes Gutenberg University (JGU), Mainz
- 2010 - 2015: Executive Director, Institute of Molecular Biology (IMB), Mainz
- Since 2000: Professor of Molecular Embryology, DKFZ, Heidelberg
- Since 1994: Head of Division "Molecular Embryology", German Cancer Research Center (DKFZ), Heidelberg
- 1990 - 1993: Postdoc, University of California Los Angeles
- 1997: Habilitation, Faculty of Biology (Zoology), University of Heidelberg
- 1990: PhD, EMBL, Heidelberg
- 1985: Diploma in Biochemistry, Free University of Berlin
Selected publications by Christof Niehrs
Musheev MU#, Baumgärtner A, Krebs L and Niehrs C# (2020) The origin of genomic N6-methyl-deoxyadenosine in mammalian cells. Nat Chem Biol, 16:630–634 (#indicates joint correspondence) Link
Niehrs C* and Luke B* (2020) Regulatory R-loops as facilitators of gene expression and genome stability. Nat Rev Mol Cell Biol, 21:167–178 (*indicates joint contribution) Link
Arab K, Karaulanov E, Musheev M, Trnka P, Schäfer A, Grummt I# and Niehrs C# (2019) GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nat Genet, 51:217–223 (#indicates joint correspondence) Link
Kirsch N, Chang LS, Koch S, Glinka A, Dolde C, Colozza G, Benitez MDJ, De Robertis EM and Niehrs C (2017) Angiopoietin-like 4 is a Wnt signaling antagonist that promotes LRP6 turnover. Dev Cell, 43:71–82.e6 Link
Schomacher L, Han D, Musheev MU, Arab K, Kienhofer S, von Seggern A and Niehrs C (2016) Neil DNA glycosylases promote substrate turnover by Tdg during DNA demethylation. Nat Struct Mol Biol, 23:116–124 Link