Project SummaryUnderstanding the molecular mechanisms that govern hematopoietic lineage specification anddifferentiation is critical for developing targeted therapies for bone marrow failure andmyeloproliferative disorders. Rcor1 (CoREST) is an established cofactor for the histonedemethylase LSD1/KDM1, however its role in regulating hematopoiesis is unknown. Using aconditional knockout model we now demonstrate that myeloerythroid differentiation isprofoundly dependent on Rcor1. The overall goal of this proposal is to the identify themechanisms by which Rcor1 regulates myelomonocytic progenitors. Specifically we will i)Determine the functions of Rcor1 in myelomonocytic progenitors and monocytes; ii) IdentifyRcor1 targets in granulocyte precursors and monocytes and iii) Determine the functions of theRcor1 target genes and pathways in myelomonocytic progenitor cell differentiation. By profilingthe transcriptional programs in Rcor1 deficient progenitors, we will identify functionally relevanttranscriptional targets of Rcor1. The results of this study will contribute to our understanding ofepigenetic regulation of normal hematopoietic progenitor cells and will likely provide importantinsights relevant to the pathogenesis of bone marrow failure syndromes and myeloproliferativedisorders.
|Effective start/end date||7/15/16 → 5/31/21|
- National Institutes of Health: $346,500.00