@article{KleinBenchellalKleffetal.2013,
  author    = {Klein, Diana and Benchellal, Mohamed and Kleff, Veronika and Jakob, Heinz G{\"u}nther and Erg{\"u}n, S{\"u}leyman},
  title     = {Hox genes are involved in vascular wall-resident multipotent stem cell differentiation into smooth muscle cells},
  series = {Scientific Reports},
  volume    = {3},
  journal   = {Scientific Reports},
  number    = {2178},
  doi       = {10.1038/srep02178},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131496},
  year      = {2013},
  abstract  = {Human vascular wall-resident CD44+ multipotent stem cells (VW-MPSCs) within the vascular adventitia are capable to differentiate into pericytes and smooth muscle cells (SMC). This study demonstrates HOX-dependent differentiation of CD44(+) VW-MPSCs into SMC that involves epigenetic modification of transgelin as a down-stream regulated gene. First, HOXB7, HOXC6 and HOXC8 were identified to be differentially expressed in VW-MPSCs as compared to terminal differentiated human aortic SMC, endothelial cells and undifferentiated pluripotent embryonic stem cells. Silencing these HOX genes in VW-MPSCs significantly reduced their sprouting capacity and increased expression of the SMC markers transgelin and calponin and the histone gene histone H1. Furthermore, the methylation pattern of the TAGLN promoter was altered. In summary, our findings suggest a role for certain HOX genes in regulating differentiation of human VW-MPSC into SMCs that involves epigenetic mechanisms. This is critical for understanding VW-MPSC-dependent vascular disease processes such as neointima formation and tumor vascularization.},
  language  = {en}
}
@article{GeyerChalmersMacKintoshetal.2013,
  author    = {Geyer, Kathrin K. and Chalmers, Iain W. and MacKintosh, Neil and Hirst, Julie E. and Geoghegan, Rory and Badets, Mathieu and Brophy, Peter M. and Brehm, Klaus and Hoffmann, Karl F.},
  title     = {Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes},
  series = {BMC Genomics},
  volume    = {14},
  journal   = {BMC Genomics},
  number    = {462},
  issn      = {1471-2164},
  doi       = {10.1186/1471-2164-14-462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121892},
  year      = {2013},
  abstract  = {Background: The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. Results: Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and 'Turbellaria') contain methylated cytosines within their genome compartments. Conclusions: Collectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology.},
  language  = {en}
}
@article{DeekenGohlkeScholzetal.2013,
  author    = {Deeken, Rosalia and Gohlke, Jochen and Scholz, Claus-Juergen and Kneitz, Susanne and Weber, Dana and Fuchs, Joerg and Hedrich, Rainer},
  title     = {DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors},
  series = {PLoS Genetics},
  journal   = {PLoS Genetics},
  doi       = {10.1371/journal.pgen.1003267},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96318},
  year      = {2013},
  abstract  = {Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene expression, physiological processes, and the development of crown gall tumors.},
  language  = {en}
}