Our research focuses on understanding development, gene regulation, and epigenetics on a genome-wide scale, in the context of evolution. This involves the design and application of algorithms, statistics, and experimental approaches.
Sequence and structure determinants of microRNA/target interactions
microRNAs are 19-24 nt long RNAs that post-transcriptionally silence their target genes by binding to the target mRNAs. microRNAs are key players in important cellular activities such as proliferation, morphogenesis, apoptosis, and differentiation. Besides an investigation of the mechanistic aspects of microRNA silencing, the elucidation of the microRNA regulatory network is a major challenge. With that, knowledge of potential targets is of highest importance.
Animal and plant microRNA targets: A number of prediction methods has contributed greatly in the generation of interesting hypotheses about possible microRNA/target relationships. Among these, RNAhybrid (Rehmsmeier et al. 2004, Krüger and Rehmsmeier 2006) is unique in offering a flexible online prediction and a thorough statistical assessment of individual binding sites, multiple binding sites, and conservation of microRNA/target relationships over multiple species. We have recently extended the scope of RNAhybrid applications to the prediction of plant microRNA targets (Alves Junior et al. 2009).
Computational analysis of cis-regulatory elements in epigenetics and development
Gene regulation is the process through which an organism effects spatial and temporal differences in gene expresion levels. DNA cis-regulatory elements are key players in this process, since it is through them that transcriptional regulation is mediated. As a consequence, knowledge of cis-regulatory elements is indispensable for the understanding of gene regulation and of the development of organisms. Among these elements are enhancers, which establish gene expression states, and Polycomb/Trithorax Response Elements (PREs), which take over from enhancers and maintain transcription states of several hundred developmentally important genes, thus establishing a memory of transcriptional history. PREs are essential to the correct identities of both stem cells and differentiated cells. Decoding regulatory networks and the study of their evolution involves the genome-wide prediction of such elements in and across species. Studying the evolution of regulatory networks beyond the scope of conserved elements remains a challenge.
Fly Polycomb/Trithorax Response Elements: We have developed a method for genome-wide single-species prediction of cis-regulatory elements and could show that, (1), the use of positive and negative training sets improves the prediction, and, (2), elements can be predicted better with paired motifs than with single motifs. Applying this method to fly Polycomb/Trithorax Response Elements on the basis of binding sites for recruiting factors, we were able to significantly expand the set of known Polycomb targets in Drosophila beyond the Hox genes (Ringrose et al. 2003). We generalised the prediction method into a versatile and easy-to-use program, jPREdictor, which lends itself conveniently to the fast prediction of any kind of cis-regulatory elements on a genome-wide scale (Fiedler and Rehmsmeier 2006). To evaluate cis-regulatory evolution, we developed an alignment-independent comparative method that is not restricted to sequence conserved elements. Applying this method to several Drosophila species showed that PRE evolution is extraordinarily dynamic (Hauenschild et al. 2008). Our study documents a novel dimension of cis-regulatory evolution and suggests that PRE elements may be a rich source of phenotypic diversity.
|Leonardo Alves Junior, Sandra Niemeier, Arne Hauenschild, Marc Rehmsmeier, Thomas Merkle
Comprehensive prediction of novel microRNA targets in Arabidopsis thaliana
( data article )
Nucleic Acids Research, 37(12):4010-21, 2009
|Gabriele Siegel, Gregor Obernosterer, Roberto Fiore, Silvia Bicker, Mette Christensen, Matthias Veith, Philipp F. Leuschner, Clara J. L. Busch, Christina Kane, Katja Hübel, Frank Dekker, Balamurugan Rengarajan, Carsten Drepper, Herbert Waldmann, Sakari Kauppinen, Michael E. Greenberg, Marc Rehmsmeier, Javier Martinez, Gerhard Schratt
A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis
( abstract )
Nature Cell Biology, 11(6):705-16, 2009
|Arne Hauenschild, Leonie Ringrose, Christina Altmutter, Renato Paro, Marc Rehmsmeier
Evolutionary Plasticity of Poycomb/Trithorax Response Elements in Drosophila Species
( data article )
PLoS Biology, 6(10):e261, 2008
|Thomas Fiedler and Marc Rehmsmeier
jPREdictor: a versatile tool for the prediction of cis-regulatory elements
( software article )
Nucleic Acids Research, 34(Web Server issue):W546-W550, 2006
|Jan Krüger and Marc Rehmsmeier
RNAhybrid: microRNA target prediction easy, fast, and flexible
( software article )
Nucleic Acids Research, 34(Web Server issue):W451-W454, 2006
|Marc Rehmsmeier, Peter Steffen, Matthias Höchsmann, Robert Giegerich
Fast and effective prediction of microRNA/target duplexes
( software supplement )
RNA, 10:1507-1517, 2004
|Leonie Ringrose, Marc Rehmsmeier, Jean-Maurice Dura, Renato Paro
Genome-Wide Prediction of Polycomb/Trithorax Response Elements in Drosophila melanogaster
( supplement software )
Developmental Cell, 5:759-771, 2003
SoftwareSoftware can be used online on or downloaded from BiBiServ, the Bielefeld Bioinformatics Server.
|RNAhybrid: Fast and effective prediction of microRNA/target duplexes ( link )|
|RNAshapes: Abstract shapes of RNA ( link )|
|jPREdictor: a Java tool for the prediction of cis-regulatory elements ( link )|
|PREdictor: Prediction of Polycomb/Trithorax Response Elements in Drosophila melanogaster ( link )|
|Phase4: Automatic evaluation of database search methods ( link )|
Marc Rehmsmeier - Last Change: 26.02.2013