Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes

Zhen, Chao Yu; Duc, Huy Nguyen; Kokotovic, Marko; Phiel, Christopher J.; Ren, Xiaojun

doi:10.1091/mbc.e14-06-1109

Cited by 37 publications

(59 citation statements)

References 65 publications

(81 reference statements)

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“…Our observations that the assembly stoichiometry of Cbx2 on chromatin is distinct between mES and differentiated cells suggest that the Cbx proteins diversify their functions during cell differentiation. Recent studies have shown that Cbx2 possesses unique characteristics during development and cell cycle progression (49,68). In a mouse zygote, Cbx2 targets PRC1 to constitutive heterochromatin in a parent-of-origin-dependent manner (68).…”

Section: Discussionmentioning

confidence: 99%

“…The plasmids (49), and pEGFP-KAP1 (50) have been described previously. The sequences encoding Eed (Addgene) and Ezh2 (Addgene) were amplified by PCR and inserted downstream of the coding sequence of fluorescence protein in pTRIPZ(M) vector (49).…”

Section: Methodsmentioning

confidence: 99%

“…The sequences encoding Eed (Addgene) and Ezh2 (Addgene) were amplified by PCR and inserted downstream of the coding sequence of fluorescence protein in pTRIPZ(M) vector (49). The sequence encoding YFP was amplified by PCR and inserted into pGEX-6P-1 vector (GE Healthcare) to generate pGEX-6P-1-YFP (monomeric YFP) and pGEX-6P-1-YFP-YFP (dimeric YFP).…”

Section: Methodsmentioning

confidence: 99%

“…Establishing Transgenic mES Cell Lines-Establishing the transgenic mES cell lines was performed according to the procedure described previously (49). Briefly, pseudo-viruses were packaged in HEK293T cells by co-transfecting with 21 g of pTRIPZ(M) containing the fusion gene, 21 g of psPAX2, and 10.5 g of pMD2.G.…”

Section: Methodsmentioning

confidence: 99%

“…After incubating with 0.1 g/ml Hoechst, cells were washed and mounted on slides with ProLong antifade reagents (P7481; Life Technologies, Inc.). The images were taken and processed as described previously (49).…”

Section: Ezh2mentioning

confidence: 99%

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Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging

Tatavosian

Zhen

Duc

et al. 2015

Journal of Biological Chemistry

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Background: Polycomb proteins control transcription by regulating chromatin structure and dynamics. Results: By developing and applying a novel Sm-ChIPi technique, we identified that one PRC1 binds multiple nucleosomes within cells, although two PRC2s can bind a single nucleosome. Conclusion: PRC1 and PRC2 complexes employ distinct mechanisms to assemble on chromatin. Significance: The cellular assembly stoichiometry provides insight into repressive polycomb chromatin structure.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ezh2mentioning

confidence: 99%

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Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging

Tatavosian

Zhen

Duc

et al. 2015

Journal of Biological Chemistry

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Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

et al. 2021

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Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins‐CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients ( N > 3000 combined), we performed pathway‐based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up‐ and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease‐specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA‐approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.

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CBX2 is a functional target of miRNA let‐7a and acts as a tumor promoter in osteosarcoma

Han

Cao

et al. 2019

Cancer Medicine

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Osteosarcoma is the most common type of primary malignant tumor of skeletal with poor prognosis in children and adolescents. Accumulating evidence indicates that CBX2 is overexpressed in multiple human neoplasm and play a critical role in tumorigenesis and progression. However, its functional role and upstream regulation mechanism in osteosarcoma remain unknown. In the present study, tissue microarray (TMA) analysis was performed to determine the association between CBX2 expression and clinical prognosis of osteosarcoma patients by immunohistochemistry. We also investigated the functional role of CBX2 using small interfering RNA (siRNA) in vitro and in vivo. Additionally, we confirmed the direct binding between CBX2 and let‐7a via qPCR, western blot and luciferase reporter assay. We found that CBX2 is dramatically upregulated in osteosarcoma tissues and high CBX2 expression was correlated with metastasis, recurrence, and chemotherapy response, as well as unfavorable prognosis in patients with osteosarcoma. Similar results were observed in a sarcoma cohort from The Cancer Genome Atlas (TCGA) dataset. Further experiments revealed that CBX2 knockdown significantly impeded osteosarcoma cell proliferation and invasion ability in vitro, and suppressed the tumor growth in tumor xenografts model. Mechanistically, we confirmed that CBX2 is a functional target of miRNA let‐7a. Overexpression of let‐7a inhibits osteosarcoma cell proliferation, which was reversed by CBX2 overexpression. Taken together, our study demonstrates that let‐7a/CBX2 plays a crucial role in osteosarcoma progression. CBX2 could serve as a promising prognostic biomarker and potential therapeutic target for osteosarcoma patients.

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Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes

Abstract: Cbx2 is immobilized at mitotic chromosomes, and the immobilization is independent of PRC1 or PRC2. Cbx2 plays important roles in recruiting PRC1 complex to mitotic chromosomes. This study provides novel insights into the PcG epigenetic memory passing down through cell divisions.

Cited by 37 publications

References 65 publications

Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging

Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

CBX2 is a functional target of miRNA let‐7a and acts as a tumor promoter in osteosarcoma

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