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Jarid2 regulates hematopoietic stem cell function by acting with Polycomb Repressive Complex 2

ABSTRACT: Polycomb Repressive Complex 2 (PRC2) has been shown to play 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 known PRC2 accessory factors in HSPCs by testing the competitive reconstitution capacity of transduced murine fetal liver cells. 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 and 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE60808 | GEO | 2015/04/02

SECONDARY ACCESSION(S): PRJNA259600

REPOSITORIES: GEO

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Jarid2 regulates hematopoietic stem cell function by acting with Polycomb Repressive Complex 2

Project description:Polycomb Repressive Complex 2 (PRC2) has been shown to play 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 known PRC2 accessory factors in HSPCs by testing the competitive reconstitution capacity of transduced murine fetal liver cells. 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 and 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. RNA-seq of jarid knockdown, suz knockdown and control from HSPC in 16 week old mice.

2015-04-02 | E-GEOD-60808 | biostudies-arrayexpress

Jarid2, a Polycomb member and target of miR-155, regulates the fates of Th17 and Treg cells

Project description:Genome-wide analysis of Jarid2, Suz12, and c-Maf binding and H3K27me3 profiling in miR-155 KO and WT Th17 performed by ChIP-seq. We found that Jarid2 and c-Maf is differentially expressed in absence of miR-155 and they compete for binding to the Il22 promoter. We highlight targets of Jarid2 and Suz12 in miR-155 KO Th17 cells that are epigenetically silenced by increased H3K27me3 status. Furthermore, genome-wide analysis through Suz12 ChIP-exo in WT and Jarid2fl/fl;CD4cre Th17 reveals defects in PRC2 recruitment in abscence of Jarid2 that results in derepression of genes in Th17 cells. Thus, one main function of miR-155 is to curb epigenetic silencing by targeting Jarid2. Examination of Jarid2, Suz12, c-Maf binding and H3K27me3 changes in miR-155 KO and WT Th17.

2014-06-01 | E-GEOD-47528 | biostudies-arrayexpress

Genome wide mapping of Jarid2 and Suz12 binding sites in mouse ES cells before and after Jarid2 depletion

Project description:We analyzed the overlap in genome wide binding sites between Jarid2 and Suz12 in mouse ES cells and find that Jarid2 and Suz12 peaks have an high degree (90%) of overlap. Moreover we analyzed the effect of Jarid2 down regulation on genome wide Suz12 binding sites and found that Loss of Jarid2 lead to the loss of 70% of Suz12 binding sites and to a 10 Fold reduction in intensity for 90% of Suz12 binding sites. Overall, these results demonstrate that Jarid2 plays an essential role for Suz12 (PRC2 complex) association to DNA. Examination of two different proteins in two different cell lines

2010-01-27 | E-GEOD-19365 | biostudies-arrayexpress

Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells

Project description:We report on mechanism of interaction between PRC2 complex and Jarid2 and their role in pluripotent cells Examination of PRC2 genomic localization by analysis of Jarid2, Ezh2, Suz12 and Jarid1a occupancy

2009-12-24 | E-GEOD-18776 | biostudies-arrayexpress

The interaction of PRC2 with RNA or chromatin is mutually antagonistic [iCLIP-Seq]

Project description:Polycomb repressive complex 2 (PRC2) maintains developmental regulator genes in a repressed state through methylation of histone H3 at lysine 27 (H3K27me3) and is necessary for cell differentiation. We and others have previously found that the PRC2 subunit Suz12 interacts with RNA in vitro and other studies have shown that Ezh2 and Jarid2 also possess RNA binding function. The interaction of PRC2 with RNA has been suggested to regulate PRC2 targeting or enzymatic activity, but the RNAs directly bound by PRC2 in cells, and the role of each PRC2 RNA binding subunit, remain unclear. We have used different CLIP techniques, which use UV-crosslinking to allow detection of direct Suz12-RNA interactions as they occur in living mouse ES cells. Suz12 binds nascent RNA and has a preference for interaction with the 3’UTR, showing it does have binding specificity in cells. RNAs bound by Suz12 at the 3’UTR encode developmental regulator genes. Suz12 remains bound to RNA upon deletion of Ezh2 or Jarid2 showing that it binds RNA independently of other PRC2 subunits. We also show that binding of Suz12 to RNA or chromatin is mutually inhibitory. Although Ezh2 and Jarid2 also bind RNA, Ezh2 and Jarid2 deletion causes an increase in Suz12 RNA binding, without changing its specificity, which reflects the loss of Suz12 from chromatin. Similarly, disruption of Suz12-RNA interactions by RNA polymerase II inhibition or RNase treatment increases Suz12 binding to chromatin. These results therefore suggest that Suz12 acts as an RNA sensor, binding to the 3’UTR of nascent RNAs and modulating the interaction of PRC2 with chromatin.

2016-05-06 | GSE66829 | GEO

The interaction of PRC2 with RNA or chromatin is mutually antagonistic [ChIP-Seq]

2016-05-06 | GSE66830 | GEO

The interaction of PRC2 with RNA or chromatin is mutually antagonistic [RNA-Seq]

2016-05-06 | GSE66814 | GEO

Genome wide mapping of Jarid2 and Suz12 binding sites in mouse ES cells before and after Jarid2 depletion

2010-01-27 | GSE19365 | GEO

Jarid2, a Polycomb member and target of miR-155, regulates the fates of Th17 and Treg cells

2014-06-01 | GSE47528 | GEO

JAZF1-SUZ12 dysregulates PRC2 recruitment and gene expression during cell differentiation

Project description:Polycomb repressive complex 2 (PRC2) maintains repression of genes specific for other cell differentiation stages through methylation of histone H3 lysine 27 (H3K27me3) and is regulated by nascent RNA. In endometrial stromal sarcoma, the PRC2 subunit SUZ12 is often fused with the transcription factor JAZF1. How JAZF1-SUZ12 affects PRC2 function and cell differentiation are unknown. Here, we show that JAZF1-SUZ12 disrupts PRC2 recruitment, gene expression and cell differentiation. The loss of the SUZ12 N-terminus in the fusion protein disrupted interaction with JARID2, EPOP and PALI1 and prevented recruitment of PRC2 from RNA to chromatin. JAZF1-SUZ12 occupied PRC2 target genes in undifferentiated cells but relocated to JAZF1 target genes during cell differentiation, altering patterns of H3K27me3 and gene expression and disrupting cell differentiation. We then performed RNA-seq in primary human cells expreesing all proteins, showing that JAZF1-SUZ12 was promoting a specific set of genes upregulated in decidualisation, while blocking immune related genes. These results reveal the defects in PRC2 function and cell differentiation caused by the JAZF1-SUZ12 fusion protein, which may underlie its role in oncogenesis.

2022-04-25 | GSE169658 | GEO

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