Unravelling transcriptional regulation through chromatin interacting proteins and SUMOylation. A functional study of FOXA1 SUMOylation, gene regulation through chromatin remodeller CHD3 and SUMO-protease SENP1 interaction and the development of a single gene locus purification system
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AbstractIn this work Ignacio Cuervo and co-workers have studied different aspects of the transcriptional regulating processes implicated in embryonic stem cell differentiation and in the regulation and dysregulation of cancer cells. The first experimental study explored a method for the study of transcription of the pluripotency gene Nanog in embryonic stem cells. The design opens up for identifying known and unknown proteins associated with the regulation of Nanog in an active and inactive state by mass spectrometry. This thesis also studied the role of SUMOylation of a transcription factor, FOXA1, involved in prostate cancer regulation. Cuervo and collaborators identified several factors that have a decreased interaction when FOXA1 is SUMOylated, as STAT3, a transcription factor regulating metastasis progression and cell survival in cancer. This novel link between FOXA1 and the differential interaction depending on SUMOylation could open for new inhibitor studies in prostate cancer. Finally, Cuervo and co-workers identified a novel function of SENP1 affecting chromatin accessibility through a novel interaction partner CHD3. This study revealed an unexplored link with deSUMOylation, chromatin remodelling, CTCF and SUMO regulation.
List of papers
|Paper I: Ignacio Cuervo, Marie Rogne, Beata Nadratowska-Wesolowska and Ragnhild Eskeland. Locus-specific chromatin purification by targeted DNA tag insertion. Manuscript. To be published. The paper is not available in DUO awaiting publishing.|
|Paper II: Ignacio Cuervo, Ankush Sharma, Marie Rogne, Odd Stokke Gabrielsen and Ragnhild Eskeland. Sumoylation modulates FOXA1 interaction with the oncogene STAT3. Manuscript. To be published. The paper is not available in DUO awaiting publishing.|
|Paper III: Fernando Rodriguez-Castañeda1, Roza Berhanu Lemma1, Ignacio Cuervo, Mads Bengtsen, Lisa Marie Moen, Marit Ledsaak, Ragnhild Eskeland and Odd Stokke Gabrielsen. The SUMO protease SENP1 and the chromatin remodeler CHD3 interact and jointly affect chromatin accessibility and gene expression, J Biol Chem (2018) 293(40), 15439-15454. DOI: /10.1074/jbc.RA118.002844. The article is included in the thesis. Also available in DUO: http://hdl.handle.net/10852/68683|