Journal article

Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2

SA Kinkel, R Galeev, C Flensburg, A Keniry, K Breslin, O Gilan, S Lee, J Liu, K Chen, LJ Gearing, DL Moore, WS Alexander, M Dawson, IJ Majewski, A Oshlack, J Larsson, ME Blewitt

Blood | Published : 2015

Abstract

Polycomb repressive complex 2 (PRC2) plays a key role in hematopoietic stem and progenitor cell (HSPC) function. Analyses of mouse mutants harboring deletions of core components have implicated PRC2 in fine-tuning multiple pathways that instruct HSPC behavior, yet how PRC2 is targeted to specific genomic loci within HSPCs remains unknown. Here we use short hairpin RNA-mediated knockdown to survey the function of PRC2 accessory factors that were defined in embryonic stem cells (ESCs) by testing the competitive reconstitution capacity of transduced murine HSPCs. We find that, similar to the phenotype observed upon depletion of core subunit Suz12, depleting Jarid2 enhances the competitive trans..

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Funding Acknowledgements

The authors thank the Walter and Eliza Hall Institute Fluorescence-Activated Cell Sorter Facility and Bioservices (particularly Keti Stoev), Samir Taoudi, and Douglas Hilton for helpful discussions, and The Dyson Bequest and The DHB Foundation for philanthropic funding (M.E.B.).This work was supported by grants from the Australian National Health and Medical Research Council (NHMRC; APP1027398) M.E.B., A.O., and I.J.M.) and Program 1016647 (W.S.A.). J.L. is supported by grants from the Swedish Research Council, the Swedish Cancer Foundation and the Swedish Pediatric Cancer Foundation. M.E.B. is a Queen Elizabeth II Fellow of the Australian Research Council (DP1096092). I.J.M., A.O. (1051481), and W.S.A. (1058344) have fellowships from the NHMRC. This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian NHMRC Research Institute Infrastructure Support Scheme.