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

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

Author(s): Kinkel, SA; Galeev, R; Flensburg, C; Keniry, A; Breslin, K; Gilan, O; Lee, S; Liu, J; Chen, K; Gearing, LJ; Moore, DL; Alexander, WS; Dawson, M; Majewski, IJ; Oshlack, A; Larsson, J; Blewitt, ME;
Details: Publication Year 2015-03-19,Volume 125,Issue #12,Page 1890-900
Journal Title: Blood
Publication Type: Journal Article
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 shRNA-mediated knockdown to survey the function of PRC2 accessory factors that were defined in ES cells, 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 transplantation capacity of both fetal and adult mouse HSPCs. Furthermore, we demonstrate that depletion of JARID2 enhances the in vitro expansion and in vivo reconstitution capacity of human HSPCs. Gene expression profiling revealed common Suz12 and Jarid2 target genes that are enriched for the H3K27me3 mark established by PRC2. These data implicate Jarid2 as an important component of PRC2 that has a central role in coordinating HSPC function.
Publisher: American Society of Hematology
Research Division(s): Cancer And Haematology; Molecular Medicine
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424268/
Publisher's Version: https://doi.org/10.1182/blood-2014-10-603969
NHMRC Grants: NHMRC/1016647, NHMRC/1027398,
ARC Grants: ARC/DP1096092,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-02-05 03:45:51

Last Modified: 2015-06-10 02:12:35