Characterization and role of UTF1 in embryonic stem and carcinoma cells. Implications for regulation of gene expression, chromatin structure and differentiation

PhD ceremony: Mr. R.P. Thummer, 11.00 uur, Doopsgezinde kerk, Oude Boteringestraat 33, Groningen

Dissertation: Characterization and role of UTF1 in embryonic stem and carcinoma cells. Implications for regulation of gene expression, chromatin structure and differentiation

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

Faculty: Mathematics and Natural Sciences

In his thesis Rajkumar Thummer has investigated the role of Undifferentiated embryonic cell Transcription Factor 1 (UTF1) in regulating specific embryonic stem (ES) and carcinoma (EC) cell properties. ES and EC cells can differentiate into (almost for EC) all cell types present in the adult organism, i.e. pluripotency. In addition, ES cells are able to proliferate indefinitely through a process called self-renewal (after division, both daughter cells are equal to the mother cell). ES cells can be derived from the inner cell mass of blastocyst embryos, a developmental stage reached 3-4 days after fertilization in mice. EC cells have been isolated from different germ cell tumors.

The UTF1 gene is highly expressed in ES and EC cells and is required for proper differentiation of these cells. Here Thummer shows that the human UTF1 protein represses gene expression and has biochemical properties very similar to core histones; essential structural chromatin proteins. In the human population, sequence variants of the UTF1 gene are present and one of these variant UTF1 genes encodes a protein with decreased histone-like properties.

When ES or EC cells are generated with elevated UTF1 levels, their ability to properly differentiate is affected, a finding of Thummer also observed in ES and EC cells with reduced UTF1 levels. Summarizing, Thummers data show that UTF1 is a key chromatin component in ES and EC cells. His data propose that UTF1 is important for a chromatin organization that prevents aberrant gene expression and required for proper initiation of lineage-specific differentiation of ES and EC cells.