AI Article Synopsis
- * The fusion of PFs, like PAX3-FOXO1, raises questions about their ability to access and modify inactive chromatin in childhood cancers like rhabdomyosarcoma (RMS).
- * This research employs a new ChIP-seq method to analyze the chromatin targeting of PAX3-FOXO1, highlighting its potential as a pioneer oncoprotein that interacts with repressed chromatin.
Article Abstract
Recent characterizations of pioneer transcription factors provide insights into their structures and patterns of chromatin recognition associated with their roles in cell fate commitment and transformation. Intersecting with these basic science concepts, identification of pioneer factors (PFs) fused together as driver translocations in childhood cancers raises questions of whether these fusions retain the fundamental ability to invade repressed chromatin, consistent with their monomeric PF constituents. This study defines the cellular and chromatin localization of PAX3-FOXO1, an oncogenic driver of childhood rhabdomyosarcoma (RMS), derived from a fusion of PFs. To quantitatively define its chromatin-targeting functions and capacity to drive epigenetic reprogramming, we developed a ChIP-seq workflow with per-cell normalization (pc-ChIP-seq). Our quantitative localization studies address structural variation in RMS genomes and reveal insights into inactive chromatin localization of PAX3-FOXO1. Taken together, our studies are consistent with pioneer function for a driver oncoprotein in RMS, with repressed chromatin binding and nucleosome-motif targeting.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346656 | PMC |
| http://dx.doi.org/10.1016/j.isci.2021.102867 | DOI Listing |
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