Research Area D - Publications 2017

Nature Chemistry, doi:10.1038/nchem.2811
Nature Chemistry, online article

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Functional antibody delivery in living cells would enable the labelling and manipulation of intracellular antigens, which constitutes a long-thought goal in cell biology and medicine. Here we present a modular strategy to create functional cell-permeable nanobodies capable of targeted labelling and manipulation of intracellular antigens in living cells. The ...

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The EMBO Journal, DOI 10.15252/embj.201695757
The EMBO Journal, online article

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Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a ...

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Nature Communications, 8, Article number: 15760, doi:10.1038/ncomms15760
Nature Communications, online article

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Histone H2AX phosphorylation is an early signalling event triggered by DNA double-strand breaks (DSBs). To elucidate the elementary units of phospho-H2AX-labelled chromatin, we integrate super-resolution microscopy of phospho-H2AX during DNA repair in human cells with genome-wide sequencing analyses. Here we identify phospho-H2AX chromatin domains in the ...

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American Association for Cancer Research, Print ISSN 0008-5472, DOI: 10.1158/0008-5472.CAN-16-1922
American Association for Cancer Research, online article

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Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of ...

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Scientific Reports, 7, Article number: 1684, doi:10.1038/s41598-017-01943-6
Scientific Reports, online article

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The bromodomain protein Brd4 is an epigenetic reader and plays a critical role in the development and maintenance of leukemia. Brd4 binds to acetylated histone tails and activates transcription by recruiting the positive elongation factor P-TEFb. Small molecule inhibitor JQ1 competitively binds the bromodomains of Brd4 and displaces the protein from acetylated ...

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Scientific Reports, 7, Article number: 1388, doi:10.1038/s41598-017-01410-2
Scientific Reports, online article

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Two-component systems are crucial for signal perception and modulation of bacterial behavior. Nevertheless, to date, very few ligands have been identified that directly interact with histidine kinases. The histidine kinase/response regulator system YehU/YehT of Escherichia coli is part of a nutrient-sensing network. Here we demonstrate that this system senses the ...

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PNAS, vol. 114 no. 20,  E3944-E3953, doi: 10.1073/pnas.1700128114
PNAS, online article

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The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) orchestrates dynamic recruitment of specific cellular machines during different stages of transcription. Signature phosphorylation patterns of Y1S2P3T4S5P6S7 heptapeptide repeats of the CTD engage specific “readers.” Whereas phospho-Ser5 and phospho-Ser2 marks are ubiquitous, ...

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Scientific Reports, 7, Article number: 1051, doi:10.1038/s41598-017-01031-9
Scientific Reports, online article

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The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of ...

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Front. Microbiol., Volume 8, Article 634, doi: 10.3389/fmicb.2017.00634
Front. Microbiol., online article

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Quorum sensing (QS) is a process enabling a bacterial population to communicate via small molecules called autoinducers (AIs). This intercellular communication process allows single cells to synchronize their behavior within a population. The marine bacterium Vibrio harveyi ATCC BAA-1116 channels the information of three AI signals into one QS cascade. Three ...

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Nature Protocols, 12, 1011–1028, doi:10.1038/nprot.2017.020
Nature Protocols, online article

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3D structured illumination microscopy (3D-SIM) is the super-resolution technique of choice for multicolor volumetric imaging. Here we provide a validated sample preparation protocol for labeling nuclei of cultured mammalian cells, image acquisition and registration practices, and downstream image analysis of nuclear structures and epigenetic marks. Using ...

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Nature Structural & Molecular Biology, 24, 341–343, doi:10.1038/nsmb.3394
Nature Structural & Molecular Biology, online article

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Chromatin-remodeling enzymes perform the formidable task of reorganizing the structure of a stable macromolecular assembly, the nucleosome. Recently published work demonstrates that the SNF2H chromatin remodeler distorts the histone octamer structure upon binding to the nucleosome, then taps into this induced plasticity to productively achieve nucleosome sliding.
 

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Molecular Plant, Volume 10, Issue 4, p575–589, http://dx.doi.org/10.1016/j.molp.2016.12.012
Molecular Plant, online article

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The translocon on the outer membrane of mitochondria (TOM) facilitates the import of nuclear-encoded proteins. The principal machinery of mitochondrial protein transport seems conserved in eukaryotes; however, divergence in the composition and structure of TOM components has been observed between mammals, yeast, and plants. TOM9, the plant homolog of yeast Tom22, ...

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Chem. Sci., 8, 3471, DOI: 10.1039/c7sc00574a
Chem. Sci., online article

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The broad substrate tolerance of tubulin tyrosine ligase is the basic rationale behind its wide applicability for chemoenzymatic protein functionalization. In this context, we report that the wild-type enzyme enables ligation of various unnatural amino acids that are substantially bigger than and structurally unrelated to the natural substrate, tyrosine, without ...

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Hum Mol Genet., 26 (8): 1522-1534; DOI: https://doi.org/10.1093/hmg/ddx057
Hum Mol Genet., online article

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DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic ...

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ACS Synth. Biol., 6 (5), pp 826–836, DOI: 10.1021/acssynbio.6b00323
ACS Synth. Biol., online article

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Natural and synthetic scaffolds support enzyme organization in complexes, and they regulate their function and activity. Here we report that CipA and CipB, two small proteins that form protein crystalline inclusions (PCIs) in the cytoplasm of Photorhabdus luminescens, can be utilized as scaffolds to efficiently incorporate exogenous proteins into PCIs. We ...

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Molecular Cell, Volume 65, Issue 4, p631–643.e4, http://dx.doi.org/10.1016/j.molcel.2017.01.023
Molecular Cell, online article

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Single-cell RNA sequencing (scRNA-seq) offers new possibilities to address biological and medical questions. However, systematic comparisons of the performance of diverse scRNA-seq protocols are lacking. We generated data from 583 mouse embryonic stem cells to evaluate six prominent scRNA-seq methods: CEL-seq2, Drop-seq, MARS-seq, SCRB-seq, Smart-seq, and ...

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Nature Chemical Biology, doi:10.1038/nchembio.2282
Nature Chemical Biology, online article

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Protein lysine methyltransferases (PKMTs) regulate diverse physiological processes including transcription and the maintenance of genomic integrity. Genetic studies suggest that the PKMTs SUV420H1 and SUV420H2 facilitate proficient nonhomologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation (me2 and me3, respectively) of lysine ...

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Molecular Microbiology, 104(1), 16–31 , doi:10.1111/mmi.13597
Molecular Microbiology, online article

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BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic ...

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MicrobiologyOpen, Volume 6, Issue 3, e00438, DOI: 10.1002/mbo3.438
MicrobiologyOpen, online article

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Two-component signal transduction constitutes the predominant strategy used by bacteria to adapt to fluctuating environments. The KdpD/KdpE system is one of the most widespread, and is crucial for K+ homeostasis. In Escherichia coli, the histidine kinase KdpD senses K+ availability, whereas the response regulator KdpE activates synthesis of the high-affinity K+ ...

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