Coordinated regulation of microRNA genes in C19MC by SETDB1

Jeon, Kyuheum; Eom, Jaemin; Min, Byungkuk; Kang, Yong‐Kook

doi:10.1016/j.bbrc.2022.11.004

Cited by 4 publications

(5 citation statements)

References 36 publications

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“…These results confirmed the functional loss of SETDB1 in this cell line. We performed reduced-representation bisulfite sequencing (RRBS) [ 32 ]. Approximately 32 million reads per sample ( n = 3 per group) were acquired (see Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings indicate that SETDB1 depletion causes hypomethylation in a large group of ZFP genes, which may affect the expression levels of corresponding ZFP genes. To test this possibility, we evaluated the expression levels of ZFP genes in the transcriptome of SETDB1-KO cells [ 32 ]. The scatter plots comparing SETDB1-KO vs. WT expression levels revealed a marked difference between DMC-associated ZFP genes and DMC-free ZFP genes (R 2 = 0.9146 vs. 0.5696; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, SETDB1 expression is relatively stable across tissues and ages [ 31 , 49 – 51 ], suggesting another mechanism that spreads and intensifies DNA methylation in chr19 ZFP genes in cancer and aging. Meanwhile, we recently observed that SETDB1 controls the largest miRNA cluster in chr19 (q13.42) in HAP1 cells [ 32 ]. Since this miRNA cluster is very close to one of the ZFP gene clusters, and the dozens of miRNA genes located there are all significantly upregulated in SETDB1-KO HAP1 cells, it will be interesting to see if the two different classes of genes in the nearby chromosomal region are subject to coordinated regulation by SETDB1 and DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, the relationship between the two epigenetic marks is less clear, as H3K9-specific histone methyltransferases (HMTases) appear to act either in conjunction with or independently of DNA methylation, depending on the target sequence [ 18 , 20 ]. All three groups of authentic H3K9-specific HMTases, SUV39H1/SUV39H2, G9A/GLP, and SETDB1, have been observed to affect DNA methylation at specific loci [ 22 , 32 , 36 , 49 ]. In this study, we did not perform an exhaustive gene-to-gene investigation for the two marks because they are not directly comparable.…”

Section: Discussionmentioning

confidence: 99%

“…To examine the differential H3K9me3 enrichments in the promoters (TSS ± 3 kb) of chr19 ZFP genes, bins with an FDR less than 0.05 were mapped to human chromosome 19 (hg38), and the bins that overlapped with the promoters of ZNF genes were colored in navy by ggplot2 (v3.4.1). The omics data used in this work, including the methylome, transcriptome, and H3K9me3 ChIP-seq, were also used in our most recent paper [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

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SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes

Kang,

Eom,

Min

et al. 2024

Mol Biol Rep

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Background SETDB1 (SET domain bifurcated-1) is a histone H3-lysine 9 (H3K9)-specific methyltransferase that mediates heterochromatin formation and repression of target genes. Despite the assumed functional link between DNA methylation and SETDB1-mediated H3K9 trimethylations, several studies have shown that SETDB1 operates autonomously of DNA methylation in a region- and cell-specific manner. This study analyzes SETDB1-null HAP1 cells through a linked methylome and transcriptome analysis, intending to explore genes controlled by SETDB1-involved DNA methylation. Methods and results We investigated SETDB1-mediated regulation of DNA methylation and gene transcription in human HAP1 cells using reduced-representation bisulfite sequencing (RRBS) and RNA sequencing. While two-thirds of differentially methylated CpGs (DMCs) in genic regions were hypomethylated in SETDB1-null cells, we detected a plethora of C2H2-type zinc-finger protein genes (C2H2-ZFP, 223 of 749) among the DMC-associated genes. Most C2H2-ZFPs with DMCs in their promoters were found hypomethylated in SETDB1-KO cells, while other non-ZFP genes with promoter DMCs were not. These C2H2-ZFPs with DMCs in their promoters were significantly upregulated in SETDB1-KO cells. Similarly, C2H2-ZFP genes were upregulated in SETDB1-null 293T cells, suggesting that SETDB1’s function in ZFP gene repression is widespread. There are several C2H2-ZFP gene clusters on chromosome 19, which were selectively hypomethylated in SETDB1-KO cells. Conclusions SETDB1 collectively and specifically represses a substantial fraction of the C2H2-ZFP gene family. Through the en-bloc silencing of a set of ZFP genes, SETDB1 may help establish a panel of ZFP proteins that are expressed cell-type specifically and thereby can serve as signature proteins for cellular identity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes

Kang,

Eom,

Min

et al. 2024

Mol Biol Rep

Self Cite

View full text Add to dashboard Cite

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Highly sensitive sensing detection of micro RNA-126 in urine using POCT-based electrochemiluminescence biosensor

Liu¹,

Huang²

2023

International Journal of Electrochemical Science

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Study on serum miR-182 as a marker for diagnosis and prognosis of cervical cancer

Gao,

Wang,

et al. 2024

THC

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BACKGROUND: Cervical cancer (CC) is a common female malignancy, with a global incidence rate second only to breast cancer. OBJECTIVE: To propose a new idea for early treatment and auxiliary diagnosis of CC by exploring the diagnostic and prognostic implications of serum miR-182 in CC. METHODS: We enrolled 70 CC patients, 35 cervical intraepithelial neoplasia (CIN) patients and 35 healthy controls (HCs), who visited The First Affiliated Hospital of Hainan Medical College Hospital between January 2015 and April 2016. miR-182 expression was quantified by real-time quantitative PCR and compared among the three groups. The correlation of serum miR-182 expression with patients’ clinical features was evaluated. The receiver operating characteristic curve (ROC) and the Kaplan-Meier method were used to evaluate the early diagnostic value and prognostic value of serum miR-182. Cox regression analysis was performed to determine serum miR-182 expression and its important role in predicting CC patients’ prognosis. RESULTS: Serum miR-182 expression was determined to be 0.345 ± 0.094, 0.369 ± 0.076, and 0.586 ± 0.157 in CC patients, CIN patients, and HCs, respectively (P< 0.001). Serum miR-182 expression had an obvious association with lymph node metastasis and pathological differentiation (P< 0.05). The area under the ROC curve (AUC) of serum miR-182 was 0.709 (95% CI: 0.622–0.795), the critical value was 0.456, the sensitivity was 81.4%, and the specificity was 52.9%. CC patients were grouped as either the low- (miR-182 < 0.3) or high-level group (miR-182 ⩾ 0.03) based on serum miR-182 levels, and a Cox regression model of OS was established. Serum miR-182 expression was identified as a factor independently influencing CC patients’ OS (P= 0.028); the death risk of the high-level group was 3.246 times that of the low-level group. CONCLUSION: Serum miR-182 expression is not only a biomarker for early diagnosis of CC, but also one of the independent factors influencing the survival and prognosis of CC patients.

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Coordinated regulation of microRNA genes in C19MC by SETDB1

Cited by 4 publications

References 36 publications

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes

Highly sensitive sensing detection of micro RNA-126 in urine using POCT-based electrochemiluminescence biosensor

Study on serum miR-182 as a marker for diagnosis and prognosis of cervical cancer

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