Elucidation of the functional role of the Q- and I-motif in the human chromatin remodeling enzyme BRG1
Helen Hoffmeister, Andreas Fuchs, Laura Strobl, Frank Sprenger, Regina Gröbner-Ferreira,Stefanie Michaelis, Petra Hoffmann, Julian Nazet, Rainer Merkl, and Gernot Längst (2019) JBC, doi: 10.1074/jbc.RA118.005685
The Snf2 proteins, comprising 53 different enzymesin humans, belong to the SF2 family. Many Snf2enzymes possess chromatin remodeling activity,requiring a functional ATPase domain consisting ofconserved motifs named Q and I-VII. These motifsform two recA-like domains, creating...
Characterizing the nuclease accessibility of DNA in human cells to map higher order structures of chromatin.
Schwartz, Németh, Diermeier, Exler H, Hansch, Maldonado, Heizinger, Merkl and Längst (2018) Nucleic Acids Res, 10.1093/nar/gky1203.
Packaging of DNA into chromatin regulates DNA ac-cessibility and consequently all DNA-dependent pro-cesses. The nucleosome is the basic packaging unitof DNA forming arrays that are suggested, by bio-chemical studies, to fold hierarchically into orderedhigher-order structures of chromatin. This organiza-tion has been recently questioned using microscopytechniques,...
Purine– and pyrimidine–triple-helix-forming oligonucleotides recognize qualitatively different target sites
Maldonado,R., Filarski,M., Grummt,I. and Längst,G. (2017) RNA, 10.1261/rna.063800.117.
Triplexes are noncanonical DNA structures, which are functionally associated with regulation of gene expression through ncRNAtargeting to chromatin. Based on the rules of Hoogsteen base-pairing, polypurine sequences of a duplex can potentially formtriplex structures with single-stranded oligonucleotides. Prediction of triplex-forming sequences by bioinformatics analyseshave revealed enrichment of potential triplex targeting sites (TTS) at regulatory elements, mainly in promoters and enhancers,suggesting a...
Hoffmeister,H., Fuchs,A., et al. (2017) Nucleic Acids Res, 45, 10534–10554.
CHD3 and CHD4 (Chromodomain Helicase DNA bind-ing protein), two highly similar representatives of theMi-2 subfamily of SF2 helicases, are coexpressed inmany cell lines and tissues and have been reportedto act as the motor subunit of the NuRD complex(nucleosome remodeling and deacetylase activities).Besides CHD proteins, NuRD contains several re-pressors like HDAC1/2, MTA2/3 and MBD2/3, argu-ing for a role as a transcriptional repressor. However,the subunit composition varies among cell- and tis-sue types and physiological...
Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning
Elisabeth Silberhorn et al., Plos Pathogens (2016)
Nucleosomes are not positioned randomly on DNA but on preferential sites with respect to the underlying DNA sequence. Histones belong to the most conserved eukaryotic proteins, as sequence dependent nucleosome positioning is an essential regulatory feature of nucleosomes, determining the accessibility of regulatory factors to DNA. We determined the biochemical properties of plasmodium histones and show that they are distinct from human forms, explaining the accessible chromatin structure of falciparum. Amino acid exchanges in the histones do...
Michael Filarsky et al., RNA Biol. 2015;12(8):864-76
The AT-hook has been defined as a DNA binding peptide motif that contains a glycine-arginine-proline (G-R-P) tripeptide core flanked by basic amino acids. Recent reports documented variations in the sequence of AT-hooks and revealed RNA binding activity of some canonical AT-hooks, suggesting a higher structural and functional variability of this protein domain than previously anticipated. Here we describe the discovery and characterization of the extended AT-hook peptide motif (eAT-hook), in which basic amino acids appear symmetrical mainly...
Josling et al., Cell Host Microbe. 2015 Jun 10;17(6):741-51
During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic...
TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning
Sarah Diermeier et al., Genome Biology 2014
Background: The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs.
Results: Using micrococcal nuclease treatment and high-throughput sequencing, we map genome-wide changes in nucleosome positioning in primary human endothelial cells stimulated with tumour necrosis factor alpha (TNFα) - a proinflammatory cytokine that signals through...
Chromatin Dynamics and Nuclear Architecture
Prof. Gernot Längst - Biochemistry III
Collaborative Research Center
Mentoring - Internationalisation