DNA Demethylation, DNA Repair and Reprogramming

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, IMB, Mainz
Since 2010: Founding & Scientific Director, Institute of Molecular Biology (IMB), Mainz; Professor at the Faculty of Biology, University of Mainz
2010-2015: Executive Director, 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

Niehrs C* and Luke B* (2020) Regulatory R-loops as facilitators of gene expression and genome stabilityNat Rev Mol Cell Biol, doi: 10.1038/s41580-019-0206-3 (*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

Koch S, Acebron SP, Herbst J, Hatiboglu G and Niehrs C (2015) Post-transcriptional Wnt signaling governs epididymal sperm maturationCell, 163:1225–1236 Link