Unknown,Transcriptomics,Genomics,Proteomics

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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. Hematopoietic stem and precursor cells freshly isolated from mice were transduced with an shRNA targeting Pcgf1 or a control shRNA. Cells were selected with puromycin for 36 h before total mRNA was isolated.

ORGANISM(S): Mus musculus

SUBMITTER: Maciej Paszkowski-Rogacz 

PROVIDER: E-GEOD-33280 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation and self-renewal of hematopoietic cells.

Ross Katharina K   Sedello Anna K AK   Todd Gabriele Putz GP   Paszkowski-Rogacz Maciej M   Bird Alexander W AW   Ding Li L   Grinenko Tatyana T   Behrens Kira K   Hubner Nina N   Mann Matthias M   Waskow Claudia C   Stocking Carol C   Buchholz Frank F  

Blood 20120312 18


The transcription factor runt-related transcription factor 1 (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 cells. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. In the presen  ...[more]

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