BET Proteins are a Key Component of Immunoglobulin Gene Expression

Shim, Jung Min; Lee, Jin S.; Russell, Kirsty; Wiegman, Coen; Barnes, Peter J.; Fear, David; Adcock, Ian M.; Durham, Andrew

doi:10.2217/epi-2016-0147

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…JQ1 reduced the binding of Oct2 to the immunoglobulin kappa locus ( IGK ) promoter, leading to a BET inhibitor-mediated decrease in immunoglobulin production in B cells. 59 In contrast to the study by Wei et al , 36 the expression of LPS-induced IL10 was decreased in regulatory B cells (B reg ) by JQ1 treatment. 79 This might represent a detrimental effect of JQ1, since B reg cells are critically involved in suppression of inflammation and known to inhibit inflammatory immune diseases including CIA.…”

Section: Introductionmentioning

confidence: 75%

“… 55 56 BRD protein members of three distinct families have been shown to interfere with the differentiation and function of Th17 cells, 34 37 52 57 58 suggesting a broad role of BRD proteins in autoimmune disorders. Furthermore, BET inhibitors affect the inflammatory responses of B cells, 59 macrophages, 10 11 13 synovial fibroblasts (SF) 15 60 61 and chondrocytes. 62 63 …”

Section: Introductionmentioning

confidence: 99%

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Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

Klein

2018

RMD Open

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The reading of acetylation marks on histones by bromodomain (BRD) proteins is a key event in transcriptional activation. Small molecule inhibitors targeting bromodomain and extra-terminal (BET) proteins compete for binding to acetylated histones. They have strong anti-inflammatory properties and exhibit encouraging effects in different cell types in vitro and in animal models resembling rheumatic diseases in vivo. Furthermore, recent studies that focus on BRD proteins beyond BET family members are discussed.

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

Klein

2018

RMD Open

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“…However, the existing literature describes a few observations that may provide some insight into these substantive differences. While not extensive, there exists literature describing the impact of epigenetic modifications on Ig gene expression [62][63][64][65][66][67][68][69] and can be altered with aging. 70 A critical hallmark of the adaptive immune response is also the magnitude of diverse antigens to which the immune system can respond.…”

Section: Discussionmentioning

confidence: 99%

Gingival tissue antibody gene utilization in aging and periodontitis

Ebersole

Linh-Trung

González

2022

J of Periodontal Research

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Objective This study used a nonhuman primate model of ligature‐induced periodontitis to document the characteristics of immunoglobulin (Ig) gene usage in gingival tissues with disease and affected by age. Background Adaptive immune responses to an array of oral bacteria are routinely detected in local gingival tissues and the systemic circulation across the human population. The level and diversity of antibody increases with periodontitis, reflecting the increased quantity of B cells and plasmacytes in the tissues at sites of periodontal lesions. Methods Macaca mulatta (n = 36) in four groups (young – ≤3 years; adolescent >3–7 years; adult – 12–15 years; aged – 17‐23 years) were used in this study. Gingival tissues were sampled at baseline (health), 2 weeks (initiation), 1 and 3 months (progression), and 5 months (resolution) of the lesion development and transcriptomic analysis included 78 Ig‐related genes. Results The results demonstrated extensive variation in Ig gene usage patterns and changes with the disease process that was substantially affected by the age of the animal. Of note was that the aged animals generally demonstrated elevated expression on multiple Ig genes even in the baseline/healthy gingival tissues. The expression levels revealed 5 aggregates of Ig gene change profiles across the age groups. The number of gene changes were greatly increased in adult animals with the initiation of disease, while the young and adolescent animals showed extensive changes with disease progression. Elevated Ig gene transcripts remained with disease resolution except in the aged animals. The response profiles demonstrated selective heavy/light change gene transcripts that differed with age and clustering of the transcript expression was dominated by the age of the animals. Conclusions The results suggested potential critical variations in the molecular aspects of Ig gene expression in gingival tissues that can contribute to understanding the kinetics of periodontal lesions, as well as the variation in episodes, rapidity of progression, and role in resolution that are impacted by age.

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“…Inhibition of BRD4 leads to the reduced accumulation of 53BP1 (a p53-binding protein required in DNA repair) and uracil DNA glycosylase (UNG, generating DNA double-strand breaks) in the CSR process (Figure 4c) [136][137][138][139]. Besides, BETis block the interaction between Brd4 and Oct2 (an immunoglobulin promoter-binding TF), decreasing immunoglobulin production and B cell proliferation rate (Figure 4c) [140].…”

Section: Adaptive Immunitymentioning

confidence: 99%

Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?

Salahong

Schwartz

Sungthong

2021

Viruses

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AIDS first emerged decades ago; however, its cure, i.e., eliminating all virus sources, is still unachievable. A critical burden of AIDS therapy is the evasive nature of HIV-1 in face of host immune responses, the so-called “latency.” Recently, a promising approach, the “Shock and Kill” strategy, was proposed to eliminate latently HIV-1-infected cell reservoirs. The “Shock and Kill” concept involves two crucial steps: HIV-1 reactivation from its latency stage using a latency-reversing agent (LRA) followed by host immune responses to destroy HIV-1-infected cells in combination with reinforced antiretroviral therapy to kill the progeny virus. Hence, a key challenge is to search for optimal LRAs. Looking at epigenetics of HIV-1 infection, researchers proved that some bromodomains and extra-terminal motif protein inhibitors (BETis) are able to reactivate HIV-1 from latency. However, to date, only a few BETis have shown HIV-1-reactivating functions, and none of them have yet been approved for clinical trial. In this review, we aim to demonstrate the epigenetic roles of BETis in HIV-1 infection and HIV-1-related immune responses. Possible future applications of BETis and their HIV-1-reactivating properties are summarized and discussed.

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BET Proteins are a Key Component of Immunoglobulin Gene Expression

Cited by 7 publications

References 41 publications

Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

Gingival tissue antibody gene utilization in aging and periodontitis

Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?

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