Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-canonical PRC1.1 licenses transcriptional response to enable Treg plasticity in immune adaptation [RNA-Seq]

ABSTRACT: Polycomb Repressive Complexes (PRCs) sustain regulatory T (Treg) cell identity through transcriptional silencing, yet their role in modulating Treg functional plasticity during immune adaptation remains unclear. Here, we identify KDM2B, a defining component of non-canonical PRC1.1, as a critical regulator for sustaining the proportion and immunosuppressive functions of active Treg (aTreg) cells without altering Treg abundance or identity. Mechanistically, PRC1.1 deposits H2AK119 monoubiquitylation (H2AK119ub1) at active promoters, surprisingly licensing aTreg transcriptional programs beyond its repressive role. Disruption of PRC1.1 via Kdm2b ablation or pharmacological inhibition with iBP, a novel selective inhibitor, reduces H2AK119ub1, blunts stimulus-dependent transcriptional activation and suppresses Treg activation. Notably, Treg-specific Kdm2b deletion in melanoma-bearing mice enhances anti-tumor immunity and synergizes with anti-PD-L1 therapy. Therefore, our study redefines H2AK119ub1 as a dual-function epigenetic mark and PRC1.1 as a molecular rheostat fine-tuning Treg adaptability, establishing PRC1.1 as a therapeutic target to decouple immune suppression in cancer while preserving Treg homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE249979 | GEO | 2026/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE249979_WTandcKO_Treg_invivo_-All_samples.GeneExpression.FPKM.txt.gz	Txt
	GSE249979_in_vitro_Treg_activation-FPKM_All_Samples.txt.gz	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Non-canonical PRC1.1 licenses transcriptional response to enable Treg plasticity in immune adaptation [CUT&TAG]

Project description:Polycomb Repressive Complexes (PRCs) sustain regulatory T (Treg) cell identity through transcriptional silencing, yet their role in modulating Treg functional plasticity during immune adaptation remains unclear. Here, we identify KDM2B, a defining component of non-canonical PRC1.1, as a critical regulator for sustaining the proportion and immunosuppressive functions of active Treg (aTreg) cells without altering Treg abundance or identity. Mechanistically, PRC1.1 deposits H2AK119 monoubiquitylation (H2AK119ub1) at active promoters, surprisingly licensing aTreg transcriptional programs beyond its repressive role. Disruption of PRC1.1 via Kdm2b ablation or pharmacological inhibition with iBP, a novel selective inhibitor, reduces H2AK119ub1, blunts stimulus-dependent transcriptional activation and suppresses Treg activation. Notably, Treg-specific Kdm2b deletion in melanoma-bearing mice enhances anti-tumor immunity and synergizes with anti-PD-L1 therapy. Therefore, our study redefines H2AK119ub1 as a dual-function epigenetic mark and PRC1.1 as a molecular rheostat fine-tuning Treg adaptability, establishing PRC1.1 as a therapeutic target to decouple immune suppression in cancer while preserving Treg homeostasis.

2026-03-31 | GSE277417 | GEO

Non-canonical PRC1.1 licenses transcriptional response to enable Treg plasticity in immune adaptation [ATAC-seq]

2026-03-31 | GSE277418 | GEO

Non-canonical PRC1.1 licenses transcriptional response to enable Treg plasticity in immune adaptation [SMART-seq]

2026-03-31 | GSE291395 | GEO

Non-canonical PRC1.1 licenses transcriptional response to enable Treg plasticity in immune adaptation [PRO-Seq]

2026-03-31 | GSE249980 | GEO

Inhibition of PRC1.1 augments Wnt signaling to promote bone remodeling

Project description:The Wnt/β-catenin signaling play critical roles in bone formation and homeostasis. However, chromatin regulatory mechanisms governing transcriptional response to the signaling are poorly understood. Polycomb group proteins are conserved epigenetic repressors safeguarding cell identity and functions, through forming multi-subunit complexes (PRCs). Their activities on histone modifications relies on interaction with the core enzyme, providing basis for therapeutic intervention. Here in aging osteoblasts, we observed a selective gain of PRC1.1 function, with KDM2B serving as a chromatin binding factor while BCOR and PCGF1 as key catalytically accessory proteins for histone H2A monoubiquitylation (H2AK119ub1). Using genetic models, we found that osteoblast-specific KDM2B inactivation significantly improves bone structure and density under steady-state conditions or scenarios of bone loss, such as aging, estrogen deficiency (following ovariectomy), or acute trauma. This improvement is attributed to the activation Wnt signaling. Transcriptomic and epigenomic analyses in purified osteoblasts demonstrate that KDM2B inactivation results in decreased H2AK119ub1 levels at the promoters of Wnt/β-catenin target genes, leading to their derepression. Through virtual screening and experimental validation, we identified a small molecule termed iBP, that specifically inhibits the interaction between BCOR and PCGF1, thereby suppressing PRC1.1 activity. Importantly, this inhibitor enhances bone formation in mouse models with bone loss. Therefore, our findings suggest that targeting PRC1.1 strengthens cellular response to Wnt signaling and may offer a promising strategy to combat bone deterioration.

2025-04-24 | GSE280429 | GEO

Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability

Project description:The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of the mSWI/SNF (BAF) complex, to Polycomb repressive complex 1 (PRC1) target genes. Here we show that the ability of SS18-SSX to occupy H2AK119ub1-rich regions is an intrinsic property of its SSX C terminus, which can be exploited by fusion to transcriptional regulators beyond SS18. Accordingly, SS18-SSX recruitment occurs in a manner that is independent of the core components and catalytic activity of BAF. Alternative SSX fusions are also recruited to H2AK119ub1-rich chromatin and reproduce the expression signatures of SS18-SSX by engaging with transcriptional activators. Variant Polycomb repressive complex 1.1 (PRC1.1) acts as the main depositor of H2AK119ub1 and is therefore required for SS18-SSX occupancy. Importantly, the SSX C terminus not only depends on H2AK119ub1 for localization, but also further increases it by promoting PRC1.1 complex stability. Consequently, high H2AK119ub1 levels are a feature of murine and human synovial sarcomas. These results uncover a critical role for SSX-C in mediating gene deregulation in synovial sarcoma by providing specificity to chromatin and further enabling oncofusion binding by enhancing PRC1.1 stability and H2AK119ub1 deposition.

2023-05-24 | GSE233376 | GEO

Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability

2023-05-24 | GSE233375 | GEO

Non-canonical PRC1.1 targets active genes independent of H3K27me3 and is essential for leukemogenesis

Project description:Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here we find that the non-canonical PRC1.1 complex, as identified by mass spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces cell proliferation in vitro and delays or even abrogates leukemogenesis in vivo in humanized xenograft models. PRC1.1 components are significantly overexpressed in primary AML CD34+ cells. Besides a set of genes that is co-targeted by PRC1 and PRC2, ChIP-seq studies show that PRC1.1 also binds a distinct set of genes that are devoid of H3K27me3 suggesting a gene regulatory role independent of PRC2. This set encompasses genes involved in metabolism, which have transcriptionally active chromatin profiles. These data indicate that PRC1.1 controls distinct gene clusters involved in unique cell biological processes required for leukemic cell viability. K562 cells were transduced with lentiviral GFP-fusion vectors encoding GFP-CBX2, PCGF1-GPF, PCGF2-GFP, PCGF4-GFP, GFP-RING1A or GFP-RING1B. K562 cells expressing GFP-fusions at relatively low levels were sorted and expanded and subsequently crosslinked. ChIP reactions were performed using the following antibodies: anti-GFP (ab290, Abcam), anti-H3K27me3 (07-449, Millipore), anti-H3K4me3 (ab8580, Abcam), anti-H2AK119ub (D27C4, Cell Signaling Technology), and anti-KDM2B (ab137547, Abcam). Furthermore, ChIP reactions were performed using primary AML CD34+ and Peripheral Blood (PB) CD34+ cells using anti-H3K27me3 (07-449, Millipore), anti-H3K4me3 (ab8580, Abcam), anti-H2AK119ub (D27C4, Cell Signaling Technology), anti-KDM2B (ab137547, Abcam).

2015-11-24 | E-GEOD-54580 | biostudies-arrayexpress

The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [RNA-seq]

Project description:Gene fusions arising from chromosomal translocations are key oncogenic drivers in soft tissue sarcomas but little is known about how they exert their oncogenic effects. Our study explores the molecular mechanisms by which the SS18-SSX fusion oncoprotein subverts epigenetic mechanisms of gene regulation to drive synovial sarcoma. Using functional genomics, we identify KDM2B – a histone demethylase and core component of a non-canonical Polycomb Repressive Complex 1 (PRC1.1) – as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands genome-wide. Via KDM2B, SS18-SSX binds and aberrantly activates expression of a series of developmentally regulated transcription factors that would otherwise be targets of polycomb-mediated repression, which is restored upon KDM2B depletion leading to irreversible mesenchymal differentiation. Thus, SS18-SSX de-regulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

2018-03-01 | GSE108928 | GEO

The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ATAC-seq]

2018-03-01 | GSE108927 | GEO