GSE117749
RNA-seq reveals novel PAF1c regulation of transcription in mouse hematopoietic progenitor cells
The Polymerase Associated Factor 1 complex (PAF1c) functions at the interface of epigenetics and gene transcription and plays a role in solid tumors and leukemia. Previous reports demonstrated that the PAF1c is required for MLL-fusion driven acute myeloid leukemia (AML) through the direct regulation of pro-leukemic target genes like Hoxa9 and Meis1. This is due to direct interactions between the PAF1c and wild type MLL or MLL fusion proteins. However, a detailed exploration of the PAF1c in normal hematopoiesis is lacking. Here, we utilize mouse genetic models to interrogate the role of the PAF1c subunit, Cdc73, in the development and maintenance of normal hematopoiesis. Using hematopoietic-specific expression of Cre recombinase, we discovered that Cdc73 is required for both embryonic and adult hematopoiesis. Here, we performed gene expression profiling (RNA-seq) in normal ckit+ HSPCs expressing Cdc73 or lacking Cdc73. Gene expression profiling in normal ckit+ HSPCs revealed differential regulation of Hoxa9 and Meis1 gene programs by CDC73 in normal hematopoietic cells compared to previously reported effects on AML cells. Overall design: Differential gene expression of genes regulated by Cdc73 in mouse hematopoietic cells. RNA-seq of cKit+ bone marrow from 3 mice with hematopoietic specific deletion of Cdc73 or 3 control mice performed on Illumina HiSeq4000