Functional connections between UTF1, chromatin structure and embryonic stem cell pluripotency

Promotie: ms. S.M. Kooistra, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Proefschrift: Functional connections between UTF1, chromatin structure and embryonic stem cell pluripotency

Promotor(s): prof.dr. P.J.M. van Haastert

Faculteit: Wiskunde en Natuurwetenschappen

During embryonic development, the fertilized egg and its early offspring have the unique capability to differentiate into all of the cell types that constitute an adult individual. These amazing proliferation and differentiation capacities of are captured in vitro by cells that can be isolated from early embryos, embryonic stem cells (ES cells). ES cells have two unique characteristics; they have the capability of unlimited cell division resulting in two identical daughter cells (self-renewal) and they have the potential to differentiate into all cell types of the adult organism (pluripotency). The thesis of Susanne Kooistra describes the role that the ‘Undifferentiated embryonic cell Transcription Factor 1’ (UTF1) protein plays in the regulation of these properties in ES cells.

Her results show that UTF1 is not involved in the regulation of ES cell self-renewal. However, UTF1 is important for the differentiation of ES cells, since reduction of UTF1 levels results in an impaired differentiation potential of these cells. Studies on the biochemical properties of the protein indicated that UTF1 is capable of transcriptional repression and that it has properties very similar to a structural component of chromatin, core histone proteins. The organization of the chromatin in the presence of UTF1 is probably important for the expression of the genes within that chromatin and, as a result, for the identity of ES cells. Furthermore, UTF1 could facilitate the rearrangement of chromatin structure and changes in expression patterns during differentiation of ES cells.