<scp>YY</scp>1 binds to the E3ʹ enhancer and inhibits the expression of the immunoglobulin <i>κ</i> gene via epigenetic modifications

Zhou, Xiaorong; Xian, Weiwei; Zhang, Jie; Zhu, Yiqing; Shao, Xiaorong; Han, Yu; Qi, Yue; Ding, Xiaoling; Wang, Xiaoying

doi:10.1111/imm.12990

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…YY1 is ubiquitously expressed in human tissues and controls various cellular mechanisms including transcriptional regulation (activation/repression), cell proliferation, DNA repair, chromatin modeling, apoptosis, autophagy, X-chromosome inactivation, recruitment of Polycomb Group (PcG) proteins and epigenetic modifications (1, 2, 10–13). YY1 has also been implicated in B cell maturation, development and immunoglobin class switch recombination (14, 15).…”

Section: Introductionmentioning

confidence: 99%

The Two Sides of YY1 in Cancer: A Friend and a Foe

2019

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Yin Yang 1 (YY1), a dual function transcription factor, is known to regulate transcriptional activation and repression of many genes associated with multiple cellular processes including cellular differentiation, DNA repair, autophagy, cell survival vs. apoptosis, and cell division. Owing to its role in processes that upon deregulation are linked to malignant transformation, YY1 has been implicated as a major driver of many cancers. While a large body of evidence supports the role of YY1 as a tumor promoter, recent reports indicated that YY1 also functions as a tumor suppressor. The mechanism by which YY1 brings out opposing outcome in tumor growth vs. suppression is not completely clear and some of the recent reports have provided significant insight into this. Likewise, the mechanism by which YY1 functions both as a transcriptional activator and repressor is not completely clear. It is likely that the proteins with which YY1 interacts might determine its function as an activator or repressor of transcription as well as its role as a tumor suppressor or promoter. Hence, a collection of YY1-protein interactions in the context of different cancers would help us gain an insight into how YY1 promotes or suppresses cancers. This review focuses on the YY1 interacting partners and its target genes in different cancer models. Finally, we discuss the possibility of therapeutically targeting the YY1 in cancers where it functions as a tumor promoter.

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Section: Introductionmentioning

confidence: 99%

The Two Sides of YY1 in Cancer: A Friend and a Foe

2019

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“…Given that pro‐inflammatory phenotype of adventitial fibroblasts from the PAH vessel are usually associated with epigenetic alterations (Gomez‐Arroyo et al, 2016; Lau et al, 2017), and YY‐1 acts predominantly as an epigenetic modulator (Infante et al, 2015; Zhou et al, 2018), we subsequently examined the alterations of histone methylation modifications of pulmonary adventitial fibroblasts by western blotting. As shown in Figure 3A, sCD40L treatment did not obviously affect the modificatory levels of H3K4me3 and H3K36me3, which are commonly considered to activate gene transcription (Guenther et al, 2007; Edmunds et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Yin Yang‐1 suppresses CD40 ligand‐CD40 signaling‐mediated anti‐inflammatory cytokine interleukin‐10 expression in pulmonary adventitial fibroblasts by promoting histone H3 tri‐methylation at lysine 27 modification on interleukin‐10 promoter

Pan

Yang

et al. 2020

Cell Biology International

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During the pathogenesis of early pulmonary arterial hypertension (PAH), pulmonary arterial adventitial fibroblast act as an initiator and mediator of inflammatory processes that predispose vessel walls to excessive vasoconstriction and pathogenic vascular remodeling. Emerging studies report that Yin Yang‐1 (YY‐1) plays important roles in inflammatory response and vascular injury. Our recent study finds that activation of CD40 ligand (CD40L)–CD40 signaling promotes pro‐inflammatory phenotype of pulmonary adventitial fibroblasts. However, whether YY‐1 is involved in CD40L–CD40 signaling‐triggered inflammatory response in pulmonary adventitial fibroblasts and its underlying mechanism is still unclear. Here, we show that soluble CD40L (sCD40L) stimulation promotes YY‐1 protein expression and suppresses anti‐inflammatory cytokine, interleukin 10 (IL‐10) expression in pulmonary adventitial fibroblasts, while YY‐1 knockdown prevents sCD40L‐mediated reduction of IL‐10 expression via enhancing IL‐10 gene transactivation. Further, we find that sCD40L stimulation significantly increases histone H3 tri‐methylation at lysine 27 (H3K27me3) modification on IL‐10 promoter in pulmonary adventitial fibroblasts, and YY‐1 knockdown prevents the effect of sCD40L on IL‐10 promoter by reducing the interaction with enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, binding to IL‐10 promoter. Moreover, we find that sCD40L stimulation promotes YY‐1 protein, but not messenger RNA (mRNA) expression, via decreasing N6‐methyladenosine methylation on YY‐1 mRNA to suppress YTHDF2‐medicated mRNA decay. Overall, this in‐depth study shows that the activation of CD40L‐CD40 signaling upregulates YY‐1 protein expression in pulmonary adventitial fibroblasts, which results in increasing YY‐1 and EZH2 binding to the IL‐10 promoter region to enhance H3K27me3 modification, eventually leading to suppression of IL‐10 transactivation. This study first uncovers the roles of YY‐1 on CD40L‐CD40 signaling‐triggered inflammatory response in pulmonary adventitial fibroblasts.

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“…International Publisher including activator protein 1 (AP1), YY1, TCF3 (E2A), and STAT5, can bind to Ei and E3ʹ in different contexts [8][9][10][11], and their roles in MYC overexpression in BL are not fully understood.…”

Section: Ivyspringmentioning

confidence: 99%

“…ChIP analysis was performed as previously described [11]. Chromatin solutions were precipitated overnight at 4 °C using c-Jun antibody or rabbit Ig control (Abcam, Cambridge, MA).…”

Section: Chromatin Immunoprecipitation Assays (Chip)mentioning

confidence: 99%

JNK/AP1 Pathway Regulates MYC Expression and BCR Signaling through Ig Enhancers in Burkitt Lymphoma Cells

et al. 2020

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In Burkitt lymphoma (BL), a chromosomal translocation by which the MYC gene is fused to an immunoglobulin (Ig) gene locus is frequently found. The translocated MYC gene is overexpressed, which is the major driver of BL tumorigenesis. Studies have shown that Ig enhancers are essential for MYC overexpression, but the involved mechanisms are not fully understood. In addition, the survival of BL cells relies on B-cell receptor (BCR) signaling, which is determined by the levels of Ig molecules expressed on the cell surface. However, whether MYC has any impact on Ig expression and its functional relevance in BL has not been investigated. Herein, we show that MYC upregulates Ig kappa (Igκ) expression in BL cells through two Igκ enhancers, the intronic enhancer (Ei) and the 3ʹ enhancer (E3ʹ). Mechanistically, by activating the JNK pathway, MYC induces the phosphorylation of c-Fos/c-Jun and their recruitment to AP1 binding sites in the Igκ enhancers, leading to the activation of the enhancers and subsequent Igκ upregulation. The AP1-mediated activation of the Igκ enhancers is also required for the expression of the translocated MYC gene, indicating positive feedback for the MYC overexpression in BL cells. Importantly, interrupting the JNK pathway inhibits both Igκ and MYC gene expression and suppresses BL cell proliferation. Our study not only reveals a novel mechanism underlying MYC overexpression in BL but also suggests that targeting the JNK pathway may provide a unique strategy to suppress BL tumorigenesis.

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YY1 binds to the E3ʹ enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications

Cited by 8 publications

References 39 publications

The Two Sides of YY1 in Cancer: A Friend and a Foe

The Two Sides of YY1 in Cancer: A Friend and a Foe

Yin Yang‐1 suppresses CD40 ligand‐CD40 signaling‐mediated anti‐inflammatory cytokine interleukin‐10 expression in pulmonary adventitial fibroblasts by promoting histone H3 tri‐methylation at lysine 27 modification on interleukin‐10 promoter

JNK/AP1 Pathway Regulates MYC Expression and BCR Signaling through Ig Enhancers in Burkitt Lymphoma Cells

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