Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell apoptosis

Li, Jian; Li, Yang; Cao, Yingying; Yuan, Meifen; Gao, Zhan; Guo, Xuemei; Zhu, Fenhua; Wang, Yunfeng; Xu, Jin

doi:10.1016/j.abb.2014.10.004

Cited by 14 publications

(19 citation statements)

References 27 publications

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“…On the other hand, CBX family proteins also have been shown to enhance gene transcription in certain cases. For example, Cbx4 enhances the expression of VEGF and promotes angiogenesis in hepatocellular carcinoma cells (Li et al, 2014a, b), which is consistent with our findings that Cbx2 enhances antiviral innate immunity by promoting the transcriptional activation of IFN-β. Therefore, it is possible that these distinct functions of Cbx2 are cell-type-specific.…”

Section: Discussionsupporting

confidence: 92%

“…As a positive regulator of IFN-β transcription activation, the Cbx2 expression pattern differs from the expression pattern of other activators that are virus-inducible (Li et al, 2014a). This difference might be explained by a fine-tuning mechanism that serves to prevent superfluous IFN-β production.…”

Section: Discussionmentioning

confidence: 99%

“…The IL-6 and IFN-β luciferase reporter plasmids have been described previously (Li et al, 2014a). Expression vectors encoding Flag-tagged Cbx2, Myc-tagged Jmjd3 and Myc-tagged IRF3 were constructed by PCR cloning into pcDNA3.1-Flag or pcDNA3.1-Myc eukaryotic expression vectors.…”

Section: Methodsmentioning

confidence: 99%

“…Accumulating evidence has demonstrated that CBX proteins play crucial roles in a variety of biological processes, such as the differentiation of stem cells, neurite development and tumor angiogenesis (Chen et al, 2017; Santanach et al, 2017; Sparmann and van Lohuizen, 2006). Recently, Cbx7 has been shown to repress activation-induced T cell apoptosis, indicating a role in the adaptive immune response (Li et al, 2014a, b). However, the role of CBX family proteins in innate immunity remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Polycomb chromobox Cbx2 enhances antiviral innate immunity by promoting Jmjd3-mediated demethylation of H3K27 at the Ifnb promoter

2018

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Polycomb chromobox (CBX) proteins regulate gene transcription by maintaining chromatin states, which guide a variety of biological processes. Now, epigenetic regulation of innate immune response is an emerging field. However, the role of CBX proteins in innate immunity remains unclear. We confirmed that the expression of CBX family proteins, especially Cbx2, was decreased in macrophages upon viral infection, and then we investigated the role of Cbx2 in the antiviral immune response. Silencing or knockdown of Cbx2 in macrophages inhibited virus-induced production of IFN-β. Furthermore, heterozygous Cbx2 knockout were susceptible to VSV challenge. Mechanistically, Cbx2 binds to and recruits Jmjd3 to the Ifnb promoter, leading to demethylation of H3K27me3 and increased transcription of IFN-β. Together, our study reveals a non-traditional function of a Cbx protein and adds new insight into the epigenetic regulation of antiviral innate immunity.Electronic supplementary materialThe online version of this article (10.1007/s13238-018-0581-0) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polycomb chromobox Cbx2 enhances antiviral innate immunity by promoting Jmjd3-mediated demethylation of H3K27 at the Ifnb promoter

2018

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“…CBX (chromobox homolog) genes are members of the PcG family, which are major epigenetic regulators. CBX8 has been described as an epigenetic transcriptional repressor involved in the inhibition of cell senescence, proliferation and metastasis of cancer cells[ 73 – 74 ] while CBX7 is involved in the modulation of cell apoptosis and gene transcription in several cell types[ 75 ]. Beyond this, CBX2 / M33 functions as a critical factor in controlling the meiotic process of male germ cells[ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of sex-related genes in the blood clam Tegillarca granosa

et al. 2017

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BackgroundBlood clams (Tegillarca granosa) are one of the most commercial shellfish in China and South Asia with wide distribution in Indo-Pacific tropical to temperate estuaries. However, recent data indicate a decline in the germplasm of this species. Furthermore, the molecular mechanisms underpinning reproductive regulation remain unclear and information regarding genetic diversity is limited. Understanding the reproductive biology of shellfish is important in interpreting their embryology development, reproduction and population structure. Transcriptome sequencing (RNA-seq) rapidly obtains genetic sequence information from almost all transcripts of a particular tissue and currently represents the most prevalent and effective method for constructing genetic expression profiles.ResultsNon-reference RNA-seq, an Illumina HiSeq2500 Solexa system, and de novo assembly were used to construct a gonadal expression profile of the blood clam. A total of 63.75 Gb of clean data, with at least 89.46% of Quality30 (Q30), were generated which was then combined into 214,440 transcripts and 125,673 unigenes with a mean length of 1,122.63 and 781.30 base pairs (bp). In total, 27,325 genes were annotated by comparison with public databases. Of these, 2,140 and 2,070 differentially expressed genes (DEGs) were obtained (T05 T08 vs T01 T02 T04, T06 T07 vs T01 T02 T04; in which T01-T04 and T05-T08 represent biological replicates of individual female and male clams, respectively) and classified into two groups according to the evaluation of biological replicates. Then 35 DEGs and 5 sex-related unigenes, in other similar species, were investigated using qRT-PCR, the results of which were confirmed to data arising from RNA-seq. Among the DEGs, sex-related genes were identified, including forkhead box L2 (Foxl2), sex determining region Y-box (Sox), beta-catenin (β-catenin), chromobox homolog (CBX) and Sex-lethal (Sxl). In addition, 6,283 simple sequence repeats (SSRs) and 614,710 single nucleotide polymorphisms (SNPs) were identified from the RNA-seq results.ConclusionsThis study provided the first complete gonadal transcriptome data for the blood clam and allowed us to search many aspects of gene sequence information, not limited to gender. This data will improve our understanding of the transcriptomics and reproductive biology of the blood clam. Furthermore, molecular markers such as SSRs and SNPs will be useful in the analysis of genetic evolution, bulked segregant analysis (BSA) and genome-wide association studies (GWAS). Our transcriptome data will therefore provide important genetic information for the breeding and conservation of germplasm.

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CBX4 promotes antitumor immunity by suppressing Pdcd1 expression in T cells

Ren,

Li,

Zhou

et al. 2023

Molecular Oncology

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E3 SUMO‐protein ligase CBX4 (CBX4), a key component of polycomb‐repressive complexes 1 (PRC1), has been reported to regulate a variety of genes implicated in tumor growth, metastasis, and angiogenesis. However, its role in T‐cell‐mediated antitumor immunity remains elusive. To shed light on this issue, we generated mice with T‐cell‐specific deletion of Cbx4. Tumor growth was increased in the knockout mice. Additionally, their tumor‐infiltrating lymphocytes exhibited impaired tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) production, with an elevated programmed cell death protein 1 (PD‐1) level. In fact, dysregulated Pdcd1 expression was observed in all major subsets of peripheral T cells from the knockout mice, which was accompanied by a functional defect in response to T‐cell receptor (TCR) stimulation. In support of a direct link between CBX4 and PD‐1, Cbx4 overexpression resulted in the downregulation of Pdcd1 expression. Epigenetic analyses indicated that Cbx4 deficiency leads to diminished accumulation of inhibitory histone modifications at conserved region (CR)‐C and CR‐B sites of the Pdcd1 promoter, namely mono‐ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3). Moreover, inhibition of either the E3 ligase activity of polycomb‐repressive complexes 1 (PRC1) or the methyltransferase activity of polycomb‐repressive complexes 2 (PRC2) restores Pdcd1 expression in Cbx4‐transfected cells. Cumulatively, this study reveals a novel function of CBX4 in the regulation of T‐cell function and expands our understanding of the epigenetic control of Pdcd1 expression.

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Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell apoptosis

Cited by 14 publications

References 27 publications

Polycomb chromobox Cbx2 enhances antiviral innate immunity by promoting Jmjd3-mediated demethylation of H3K27 at the Ifnb promoter

Polycomb chromobox Cbx2 enhances antiviral innate immunity by promoting Jmjd3-mediated demethylation of H3K27 at the Ifnb promoter

Transcriptome analysis of sex-related genes in the blood clam Tegillarca granosa

CBX4 promotes antitumor immunity by suppressing Pdcd1 expression in T cells

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