DNA Demethylation, DNA Repair and Reprogramming

DNA methylation signatures are currently the best predictor of organismic age; this is referred to as the epigenetic clock. DNA methylation is thought to play a critical role in the ageing process. It is therefore important to understand how DNA methylation is regulated.   

DNA methylation can be reversed by enzymatic demethylation, a process that is still incompletely understood. We have shown that growth arrest and DNA damage 45a (Gadd45a) is a key player in active DNA demethylation and acts via DNA repair. The goal of our research is to analyse the mechanism of DNA demethylation and the role of Gadd45 in development.

DNA demethylation of target genes by Gadd45a is a highly selective process: it is gene-specific, and typically affects specific mCpGs within the gene. This specificity raises a series of questions: what determines the target site specificity of DNA demethylation? Is there a relationship between site-specific DNA demethylation and the epigenetic landscape? What are the cofactors involved? We strive to answer these questions using a combination of biochemistry, molecular biology, as well as cell biology techniques.

Research website

Positions held

  • 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

Education

  • 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 cellsNat 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 stabilityNat 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 promotersNat Genet, 51:217–223 (#indicates joint correspondence) Link

Kirsch N, Chang L-S, 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 turnoverDev 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 demethylationNat Struct Mol Biol, 23:116–124 Link