Epigenetic maintenance of oncofetal identity in infant AML

The maintenance of oncofetal gene expression is a hallmark of infant AML, yet the epigenetic regulation driving this aberrant program remains unclear. To elucidate these networks, we will perform unbiased CROP-Seq alongside a focused analysis of PRC2 and SWI/SNF, two opposing epigenetic complexes in hematopoietic development. Using CRISPR-based knock-ins, we will fluorescently label the catalytic subunits EZH2 and SMARCA2/4, enabling flow cytometry-based CRISPR screens to identify regulatory mechanisms at post-transcriptional and post-translational levels. By integrating the analysis with IP-MS and CUT&RUN, we will dissect the composition and deposition of these complexes, constructing a comprehensive map of their roles in infant AML. Ultimately, this work will reveal how oncofetal epigenetic regulation is shaped and maintained, particularly by PRC2 and SWI/SNF, to drive AML pathogenesis, and will guide the development of epigenetic therapies that target the oncofetal state.

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Artikel online veröffentlicht:
09. Mai 2025