[R01] A stalled chromatin regulatory network that mediates the oncogenic activity of Meningioma-1
Ente: National Cancer Institute
Scadenza: 2027-03-31
Importo max: 438.480 EUR
Paese: US
Descrizione
PROJECT SUMMARY
High expression of the transcriptional co-activator Meningioma-1 (MN1) is common in AML, and associated
with a poor prognosis. Forced expression of MN1 in murine hematopoietic progenitors induces an aggressive
leukemia. We recently discovered that the primary interaction partner of MN1 is the BAF nucleosome-
positioning complex. MN1 stabilizes BAF on chromatin. MN1 binding is associated with sustained active
enhancer chromatin at enhancers regulating a hematopoietic stem/progenitor program. We hypothesize that
MN1 stabilizes promoter-enhancer contacts at these sites through a BAF dependent mechanism. The goal
of this project is to uncover the molecular mechanism of MN1-mediated leukemic transformation. A better
understanding of how MN1 causes leukemia may identify opportunities for targeted therapies in a patient
population who is failing conventional AML therapy.
Istituzione: CHILDREN'S HOSP OF PHILADELPHIA
PI: KATHRIN M BERNT
Progetto: 5R01CA262260-05
Settori: National Cancer Institute
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