November 3, 2021
After careful review of over 80 submissions, Arima Genomics is pleased to announce the recipient of the 2021 Promoter Capture Research Grant. Congratulations to the Brian Dynlacht Lab at New York University for being selected as our grant recipient!
The Dynlacht lab studies transcriptional regulation of the mammalian cell cycle.
About The Project: Examining Abnormal Chromatin Topology in Rhabdomyosarcomas
Alveolar rhabdomyosarcoma (ARMS) is among the most aggressive pediatric soft tissue sarcomas, with a poor survival outcome as the disease advances.
The chromosomal translocation that results in a Pax7:Fkhr fusion event, a genetic feature of most ARMS tumors, is believed to play a key role in the molecular gain of function that disables a muscle development program and favors tumor formation by blocking the affected cells in a myoblast- or stem cell-like proliferative state.
Our approach will characterize the chromatin remodeling events mediated by the PAX7-FOXO1 translocation in muscle progenitor cells and ARMS cell lines and identify targets primed by aberrant PAX7-FOXO1 transcriptional activities. We will test the hypothesis that ARMS tumors are locked in a chromatin conformation that resembles muscle stem cells by assessing genome-wide changes in chromatin organization induced by expression of PAX7-FOXO1.
Using Hi-C and promoter capture (pCHiC) to generate 3D chromatin conformation maps, we will assess the impact of the fusion protein on overall chromatin topology and gene expression during the early phases of cellular transformation. pCHiC will allow us to investigate the functional impact of PAX7-FOXO1 on enhancer-promoter interactions and focus on the resulting gene expression events that subvert the differentiation program.
It will be exciting to examine abnormal chromatin topology in rhabdomyosarcomas using the promoter capture assay system from Arima.