The study of molecular mechanisms that govern cellular differentiation and fate is key to the understanding of development, metabolism but also to the understanding of carcinogenesis. This research axis seeks to address the role of sumoylation-mediated gene control during cellular differentiation with a primary focus on adipose stem cells. Indeed, the global rise of the obesity epidemic and associated diseases such as diabetes and cancer has rendered indispensable the study of adipose tissue formation and biology. We use state of the art high-throughput methods (ChIP-seq, RNA-seq, MS, Confocal microscopy, etc.) and classical biochemistry to identify the dynamics of chromatin-bound factors’ sumoylation during adipocyte differentiation in human adipose stem cells, mouse 3T3L1 cells and mouse models.
Academic interest: Transcriptional and epigenetic regulation of cell fate and identity
Dynamic remodeling of the SUMO-chromatin landscape during cellular differentiation
Ramos-Alonso L, Holland P, Le Gras S, Zhao X, Jost B, Bjørås M, Barral Y, Enserink JM and Chymkowitch P (2022). Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis. BioRxiv: https://biorxiv.org/cgi/content/short/2022.05.11.491439v1
Zhao X, Hendriks IA, Le Gras S, Ye T, Nguéa P A, Ramos-Alonso L, Flor Lien G, Klungland A, Jost B, Enserink JM, Nilsen ML and Chymkowitch P (2022). Waves of sumoylation support transcription dynamics during adipocyte differentiation. Nucleic Acids Res. Feb 22;50(3):1351-1369.
Garcia I, Munoz S, Ramos-Alonso L, Andersen AN, Zimmermann C, Erikson J, Bøe SO, Kaferle P, Papamichos-Chronakis M, Chymkowitch P, Enserink JM (2021). Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway. Cell Reports 37, 110186, December 28
Nguéa P A, Robertson J, Herrera MC, Chymkowitch P, Enserink JM (2019). De-sumoylation of RNAPIII Lies at the Core of the Sumo-Stress Response in yeast. J. Biol. Chem. Dec 06; 294: 18784
Kruitwagen T*, Chymkowitch P*, Denoth-Lippuner A, Enserink JM, Barral Y (2018). Centromeres license the mitotic condensation of yeast chromosome arms. Cell Oct 18;175(3):780-795.e15
Herrera MC, Chymkowitch P, Robertson J, Eriksson J, Bøe SO, Enserink JM (2018). Cdk1 Gates Cell Cycle-Dependent tRNA Synthesis by Regulating RNA Polymerase III Activity. Nucleic Acids Res. Dec 14; 46 (22), 11698-11711
Chymkowitch P, Nguéa P A, Aanes H, Robertson J, Klungland A, Enserink JM (2017). TORC1-dependent sumoylation of Rpc82 promotes RNA polymerase III assembly and activity. Proc Natl Acad Sci U S A Jan 31;114(5):1039-1044
Chymkowitch P, Nguéa P A, Aanes H, Koehler CJ, Thiede B, Lorenz S, Meza-Zepeda LA, Klungland A, Enserink JM (2015). Sumoylation of Rap1 Mediates the Recruitment of TFIID to Promote Transcription of Ribosomal Protein Genes. Genome Res. Jun;25(6):897-906
Chymkowitch P, Eldholm V, Lorenz S, Zimmermann C, Lindvall JM, Bjørås M, Meza-Zepeda LA, Enserink JM (2012). Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes. Proc Natl Acad Sci U S A Jun 26;109(26):10450-5
Chymkowitch P, Le May N, Charneau P, Compe E, Egly JM (2011). The phosphorylation of the androgen receptor by TFIIH directs the ubiquitin/proteasome process. EMBO J. Feb 2;30(3):468-79
Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, Coin F, Egly JM, Tanaka K (2007). XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: Implications for Cokayne syndrome in XP-G/CS patients. Mol. Cell Apr 27;26(2):231-43