Transcriptomics

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Gene regulation in hematopoietic cells by Pcgf1 in a Runx1 null background


ABSTRACT: The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE33280 | GEO | 2012/06/18

SECONDARY ACCESSION(S): PRJNA149081

REPOSITORIES: GEO

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