Molecular mechanisms during reprogramming lecture

The fourth lecture looked at the different reprogramming processes (including nuclear transfer, expression of OKSM transcription factors, somatic-ES cell fusions) and recent studies defining the steps involved in each of these processes. The genetic and biochemical data obtained suggest that epigenetics acts as a barrier to reprogramming. In fact, it seems that chromatin acts as a brake on forced changes in gene expression. Molecular mechanisms such as DNA methylation, histone modifications and other epigenetic factors have been discussed in the context of developmental and induced reprogramming. Different mechanisms emerge: it seems that histone variants play an important role in reprogramming by nuclear transfer, whereas natural reprogramming in the germline requires a loss of methylation of lysine 9 of histone H3 (H3K9me2), the epigenetic mark classically associated with heterochromatin. The dynamics of DNA methylation were also discussed in Professor Wolf Reik's seminar. At the end of the lecture, the role of transcription factors in reprogramming was reassessed in the light of recent data indicating that cells can be "trans-differentiated" (i.e. switch from one cell fate to another, simply by forced expression of one or more appropriate transcription factors).