Pietro Vella

During my Ph.D. I have carried out two projects. The first one was focused on the Yin Yang1 (YY1) transcription factor, an essential regulator of mouse embryogenesis, with the aim to characterize its role in Polycomb recruitment to chromatin in mammalian cells. In this project I showed that in mouse embryonic stem cells Yy1 has genomewide Polycomb independent activities and binds chromatin in close proximity of the transcription start site of highly expressed genes. In general Yy1 has a dual transcriptional regulatory function, whereas it positively influences biogenesis of several small noncoding RNAs. Finally, Yy1 extensively shares genome wide binding properties with Mycrelated transcription factors and their coordinated binding at promoters potentiates gene expression, proposing YY1 as an active component of the Myc transcription network that links embryonic stem cells to cancer cells.
The second project was aimed to elucidate the nuclear functions of the Olinked N acetylglucosamine (O-GlcNAc) transferase (Ogt), an enzyme essential for mouse development that catalyzes glycosylation both on nuclear and cytoplasmic proteins in several cell types. My data found that the teneleven translocation (TET) proteins Tet1 and Tet2 are the main partners of nuclear Ogt in ES cells. At a genomewide level, Ogt preferentially associates with Tet1 in close proximity of transcription start sites rich in cytosine/guanine dinucleotides (CpG). These regions are characterized by low levels of DNA modification, suggesting a link between Tet1 and Ogt activities in regulating CpG island methylation. Finally, Tet1 functions as the main chromatin recruiter of Ogt, which in turns regulates Tet1 activity. Taken together, these data characterized how Olinked glycosylation is recruited to chromatin and interacts with the activity of 5methylcytosine hydroxylases.