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Publication : DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells.

First Author  Elabd C Year  2013
Journal  J Cell Biol Volume  203
Issue  1 Pages  73-85
PubMed ID  24127215 Mgi Jnum  J:207865
Mgi Id  MGI:5559829 Doi  10.1083/jcb.201307110
Citation  Elabd C, et al. (2013) DNA methyltransferase-3-dependent nonrandom template segregation in differentiating embryonic stem cells. J Cell Biol 203(1):73-85
abstractText  Asymmetry of cell fate is one fundamental property of stem cells, in which one daughter cell self-renews, whereas the other differentiates. Evidence of nonrandom template segregation (NRTS) of chromosomes during asymmetric cell divisions in phylogenetically divergent organisms, such as plants, fungi, and mammals, has already been shown. However, before this current work, asymmetric inheritance of chromatids has never been demonstrated in differentiating embryonic stem cells (ESCs), and its molecular mechanism has remained unknown. Our results unambiguously demonstrate NRTS in asymmetrically dividing, differentiating human and mouse ESCs. Moreover, we show that NRTS is dependent on DNA methylation and on Dnmt3 (DNA methyltransferase-3), indicating a molecular mechanism that regulates this phenomenon. Furthermore, our data support the hypothesis that retention of chromatids with the "old" template DNA preserves the epigenetic memory of cell fate, whereas localization of "new" DNA strands and de novo DNA methyltransferase to the lineage-destined daughter cell facilitates epigenetic adaptation to a new cell fate.
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