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Epigenetic modifications : ウィキペディア英語版
Epigenetics in stem-cell differentiation

Embryonic stem cells are capable of self-renewing and differentiating to the desired fate depending on its position within the body. Stem cell homeostasis is maintained through epigenetic mechanisms that are highly dynamic in regulating the chromatin structure as well as specific gene transcription programs. Epigenetics has been used to refer to changes in gene expression, which are heritable through modifications not affecting the DNA sequence.
The mammalian epigenome undergoes global remodeling during early stem cell development that requires commitment of cells to be restricted to the desired lineage. There has been multiple evidence suggesting that the maintenance of the lineage commitment of stem cells are controlled by epigenetic mechanisms such as DNA methylation, histone modifications and regulation of ATP-dependent remolding of chromatin structure.〔 Based on the ''histone code'' hypothesis, distinct covalent histone modifications can lead to functionally distinct chromatin structures that influence the fate of the cell.
This regulation of chromatin through epigenetic modifications is a molecular mechanism that will determine whether the cell will continue to differentiate into the desired fate. A research study performed by ''Lee et al.'' examined the effects of epigenetic modifications on the chromatin structure and the modulation of these epigenetic markers during stem cell differentiation through in vitro differentiation of murine embryonic stem (ES) cells.
==Experimental background==

Embryonic stem cells exhibit dramatic and complex alterations to both global and site-specific chromatin structures. ''Lee et al.'' performed an experiment to determine the importance of deacetylation and acetylation for stem cell differentiation by looking at global acetylation and methylation levels at certain site-specific modification in histone sites ''H3K9'' and ''H3K4''. Gene expression at these histones regulated by epigenetic modifications is critical in restricting the embryonic stem cell to desired cell lineages and developing cellular memory.
For mammalian cells, the maintenance of cytosine methylation is catalyzed by DNA methyltransferases and any disruption to these methyltransferases will cause a lethal phenotype to the embryo. Cytosine methylation is examined at ''H3K9'', which is associated with inactive heterochromatin and occurs mainly at CpG dinucleotides while global acetylation is examined at ''H3K4'', which is associated with active euchromatin. The mammalian zygotic genome undergoes active and passive global cytosine demethylation following fertilization that reaches a minimal point of 20% CpG methylation at the blastocyst stage to which is then followed by a wave of methylation that reprograms the chromatin structure in order to restore global levels of CpG methylation to 60%.〔 Embryonic stem cells containing reduced or elevation levels of methylation are viable but unable to differentiate and therefore require critical regulation of cytosine methylation for mammalian development.

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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