Research Focus
I investigate how regulatory DNA elements, called enhancers, control the activation of PPARG, the master regulator of human adipocyte differentiation, and how enhancer networks govern cell fate decisions during adipogenesis.
Key Findings
- Identified a highly connected enhancer community at the PPARG locus that is silent in progenitor cells and becomes activated during adipogenesis.
- Used genome editing to delete individual enhancers from the PPARG enhancer network, showing that several are required for PPARG2 activation and acquisition of the adipocyte phenotype.
- Demonstrated that enhancers act in a non-redundant and cooperative manner to activate PPARG2 through both cis cooperativity between enhancers and trans cooperativity via PPARγ-mediated feedback activation.
- Showed that key PPARG enhancers are active in human adipose tissue and overlap with cardiometabolic disease-associated genetic variants.
Key publications:
Extensive enhancer crosstalk controls PPARG2 activation during adipogenesis
Anna Cetnarowska*, Mette Hyldahl*, Marcus Nygård, Hesam Dashti, Kaja Madsen, Maria S. Madsen, Laura K. Holm, Vallari Shukla, Esra Durmaz Mitchell, Alexander Rauch, Jesper G. S. Madsen, Melina Claussnitzer and Susanne Mandrup. Manuscript in preparation, *These authors contributed equally.
Interplay between regulatory elements and chromatin topology in cellular lineage determination
Vallari Shukla*, Anna Cetnarowska*, Mette Hyldahl* and Susanne Mandrup. Trends in Genetics, 2022, *These authors contributed equally.
Grants:
The PhD fellowship within Enhpathy Consortium under the Horizon Europe Marie Sklodowska-Curie Actions (MSCA) Doctoral Network.
Contact Information
- Email: acetnarowska@bmb.sdu.dk
- LinkedIn: https://www.linkedin.com/in/anna-cetnarowska-ba9056157/