Transcription Factors

Transcription factors are critical components that control the "stemness" properties of these cells. Three transcription factors, OCT4, SOX2, and NANOG, cooperate to ensure the self-renewal and pluripotency of ES cells (Boyer, Lee et al. 2005; Loh, Wu et al. 2006). These factors are highly expressed in undifferentiated ES cells. In addition, chromatin methylation is carried out through two major repressive pathways: Polycomb group (PcG) repressive complexes and promoter DNA methylation, both of which can modulate the fate of ES cells (Christophersen-and-Kristian-Helin 2010).

DNA Modifications

Chemical modification of DNA and histones (proteins that surround DNA) occurs frequently during stem cell differentiation in regulating gene activity. Methylation of specific sites in the sequence of DNA is a common mechanism for a cell to turn off protein synthesis of a specific protein. In human cells, chemical modifications, such as DNA methylation, typically occur at the cytosine base pair of DNA. In addition, chemical modification of the proteins that surround DNA, such as histones, is another method for cells to regulate the activity of specific genes. Methylation of the N-terminal tails of histone proteins that surround the DNA molecules is an effective method to silence a gene.

Epigenetics

Epigenetics is a hereritable process and differs from Mendelian genetics. In Medelian genetics changes in the base pair sequence of a gene can be a critical determinant of its activity. At first glance epigenetic trans-generational inheritance of acquired characteristics is reminiscent of a theory of genetics proposed by Jean-Baptiste Lamarck [for example, the giraffe acquired a long neck over generations because of evolutionary pressure to reach the highest branches to obtain its natural food, leaves; i.e., they stretched their necks all the time and gradually this led to changes in the tissues (muscle, bone) that resulted in longer necks.) In contrast, Darwinian theory of natural selection would instead say that shorter-necked giraffes, unable to reach leaves in specific habitats, would die out, and long-necked giraffes would become the dominant type because they survived and passed on their genes. In fact, the current underlying mechanisms of epigenetics provide scientific evidence how environment can trigger heritable changes. There is ample evidence in animals and even in human beings that environmental factors shape health and disease via epigenetic mechanisms that mediate gene-environment interactions. According to Dr. Moshe Szyf, a leading geneticist, epigenetics is a physiological mechanism by which the genome senses the world and changes itself (Berreby 2011).

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Epigenetic Mechanisms, via Wikimedia Commons

For more information on epigenetics, view the following videos produced by Albert Einstein College of Medicine/Montefiore Medical Center, featuring Dr. John Greally.







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