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Hodges, E.; Molaro, A.; Dos Santos, C.O.; Thekkat, P.; Song, Q.; Uren, P.J.; Park, J.; Butler, J.; Rafii, S.; McCombie, W.R.; Smith, A.D.; Hannon, G.J. |
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Title |
Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment |
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Journal Article |
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Year |
2011 |
Publication |
Molecular cell |
Abbreviated Journal |
Mol Cell |
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Volume |
44 |
Issue |
1 |
Pages |
17-28 |
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Abstract |
DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates. |
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1097-4164 |
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WP5 In vitro |
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PMID: 21924933 |
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UNIBAS @ david.schuermann @ Hodges2011 |
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75 |
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Ji, H.; Ehrlich, L.I.; Seita, J.; Murakami, P.; Doi, A.; Lindau, P.; Lee, H.; Aryee, M.J.; Irizarry, R.A.; Kim, K.; Rossi, D.J.; Inlay, M.A.; Serwold, T.; Karsunky, H.; Ho, L.; Daley, G.Q.; Weissman, I.L.; Feinberg, A.P. |
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Title |
Comprehensive methylome map of lineage commitment from haematopoietic progenitors |
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Journal Article |
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Year |
2010 |
Publication |
Nature |
Abbreviated Journal |
Nature |
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Volume |
467 |
Issue |
7313 |
Pages |
338-342 |
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Keywords |
Animals; Cell Line; *Cell Lineage/genetics; CpG Islands/genetics; *DNA Methylation/genetics; Epigenesis, Genetic; Gene Expression Profiling; Genome/genetics; *Hematopoiesis/genetics; Hematopoietic Stem Cells/*cytology/*metabolism; Lymphocytes/cytology/metabolism; Metabolome; Metabolomics; Mice; Myeloid Cells/cytology/metabolism; Pluripotent Stem Cells/cytology/metabolism |
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Abstract |
Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions. |
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1476-4687 |
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WP5 In vitro |
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PMID: 20720541 |
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UNIBAS @ david.schuermann @ Ji2010 |
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76 |
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Buffler, P.; Kwan, M.; Reynolds, P.; Urayama, K. |
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Title |
Environmental and Genetic Risk Factors for Childhood Leukemia: Appraising the Evidence |
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Journal Article |
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2005 |
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Cancer Investigation |
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LCNV |
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23 |
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1 |
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60-75 |
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ISSN |
0735-7907 |
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WP9 Epidemiology |
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IARC @ ErdmannF @ |
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84 |
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Juutilainen, J.; Hoyto, A.; Kumlin, T.; Naarala, J. |
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Title |
Review of possible modulation-dependent biological effects of radiofrequency fields |
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Journal Article |
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Year |
2011 |
Publication |
Bioelectromagnetics |
Abbreviated Journal |
Bioelectromagnetics |
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32 |
Issue |
7 |
Pages |
511-534 |
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The biological effects of modulated radiofrequency (RF) electromagnetic fields have been a subject of debate since early publications more than 30 years ago, suggesting that relatively weak amplitude-modulated RF electromagnetic fields have specific biological effects different from the well-known thermal effects of RF energy. This discussion has been recently activated by the increasing human exposure to RF fields from wireless communication systems. Modulation is used in all wireless communication systems to enable the signal to carry information. A previous review in 1998 indicated that experimental evidence for modulation-specific effects of RF energy is weak. This article reviews recent studies (published after 1998) on the biological effects of modulated RF fields. The focus is on studies that have compared the effects of modulated and unmodulated (continuous wave) RF fields, or compared the effects of different kinds of modulations; studies that used only one type of signal are not included. While the majority of recent studies have reported no modulation-specific effects, there are a few interesting exceptions indicating that there may be specific effects from amplitude-modulated RF fields on the human central nervous system. These findings warrant follow-up studies. |
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ISSN |
1521-186X |
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WP5 In vitro |
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PMID: 21480304 |
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UNIBAS @ david.schuermann @ Juutilainen2011 |
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77 |
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Author |
Kroupova, J.; Bartova, E.; Fojt, L.; Strasak, L.; Kozubek, S.; Vetterl, V. |
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Title |
Low-frequency magnetic field effect on cytoskeleton and chromatin |
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Journal Article |
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Year |
2007 |
Publication |
Bioelectrochemistry |
Abbreviated Journal |
Bioelectrochemistry |
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70 |
Issue |
1 |
Pages |
96-100 |
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Keywords |
Cell Line, Tumor; Centromere; Chromatin/chemistry/genetics/*metabolism; Chromosomes, Human, Pair 8/genetics/metabolism; Cytoskeleton/*metabolism; *Electromagnetic Fields; Humans |
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Abstract |
The effect of magnetic fields on the living systems is studied in vivo or in vitro in very broad spectrum of organisms, cells and tissues. The mechanism of their acting is not known until now. We studied low-frequency magnetic field effect on cytoskeleton and on the structure of chromatin in human cells. We used cell line of small lung carcinoma (A549) and the effects of magnetic field on cytoskeleton and higher-order chromatin structure were analyzed 96 h of magnetic field exposure. Magnetic field generated by the cylindrical soil was homogenous and the cells were cultivated at 37 degrees C in humidified atmosphere containing 5% CO(2). Magnetic field induction was B(m)=2 mT and the net frequency f=50 Hz. In such affected and control cells the F-actin was estimated using FITC-conjugated Phalloidin and mitochondria were studied using MitoTracker (Molecular Probes). Images of cytoskeleton and genetic loci were acquired using confocal microscopy and analysis was performed by FISH 2.0 software. Slight morphological changes of F-actin filaments and mitochondria were observed in affected cells and nuclear condensation was found. These effects could be related to the process of cell death apoptosis probably induced by magnetic field. The studies aimed at centromeric heterochromatin (9cen) did not show statistically significant changes. Therefore, we suggest that magnetic field has no influence on higher order chromatin structure but certain changes could be observed on the level of cytoskeleton. However, these statements need a thorough verification. Our preliminary experiments will be extended and the effect of magnetic field on another structures of cytoskeleton and cell nuclei will be further studied. |
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ISSN |
1567-5394 |
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WP5 In vitro |
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PMID: 16713375 |
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Call Number |
UNIBAS @ david.schuermann @ Kroupova2007 |
Serial |
78 |
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