Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection

Funata, Sayaka; Matsusaka, Keisuke; Yamanaka, Ryota; Yamamoto, Shozo; Okabe, Atsushi; Fukuyo, Masaki; Aburatani, Hiroyuki; Fukayama, Masashi; Kaneda, Atsushi

doi:10.18632/oncotarget.19423

Cited by 30 publications

(24 citation statements)

References 37 publications

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“…It also remains unclear how promoter regions of each gene are methylated after H. pylori infection. A previous study identified DNA methylation-sensitive genes and DNA methylation-resistant genes [39]. DNA methylation-sensitive genes, including CDKN2A, are methylated in the whole promoter regions by EBV infection, whereas DNA methylation-resistant genes methylated only in the surrounding of promoter regions.…”

Section: Epigenetic Aberrant In Gastric Cancermentioning

confidence: 99%

DNA Methylation and Genetic Aberrations in Gastric Cancer

et al. 2020

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Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. GC is a pathologically and molecularly heterogeneous disease. DNA hypermethylation in promoter CpG islands causes silencing of tumor-suppressor genes and thus contributes to gastric carcinogenesis. In addition, various molecular aberrations, including aberrant chromatin structures, gene mutations, structural variants, and somatic copy number alterations, are involved in gastric carcinogenesis. Summary: Comprehensive DNA methylation analyses revealed multiple DNA methylation patterns in GCs and classified GC into distinct molecular subgroups: extremely high-methylation epigenotype uniquely observed in GC associated with Epstein-Barr virus (EBV), high-methylation epigenotype associated with microsatellite instability (MSI), and low-methylation epigenotype. In The Cancer Genome Atlas classification, EBV and MSI are extracted as independent subgroups of GC, whereas the remaining GCs are categorized into genomically stable (GS) and chromosomal instability (CIN) subgroups. EBV-positive GC, exhibiting the most extreme DNA hypermethylation in the whole human malignancies, frequently shows CDKN2A silencing, PIK3CA mutations, PD-L1/2 overexpression, and lack of TP53 mutations. MSI, exhibiting high DNA methylation, often has MLH1 silencing and abundant gene mutations. GS is generally a diffuse-type GC and frequently shows CDH1/RHOA mutations or CLDN18–ARHGAP fusion. CIN is generally an intestinal-type GC and frequently has TP53 mutations and genomic amplification of receptor tyrosine kinases. Key Messages: The frequency and targets of genetic aberrations vary depending on the epigenotype. Aberrations in the genome and epigenome are expected to synergistically interact and contribute to gastric carcinogenesis and comprehensive analyses of those in GCs may help elucidate the mechanism of carcinogenesis.

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Section: Epigenetic Aberrant In Gastric Cancermentioning

confidence: 99%

DNA Methylation and Genetic Aberrations in Gastric Cancer

et al. 2020

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“…The research indicated that the most HCNES, de ned as bivalent domains including a large H3K27me3-modi ed region encompassing a smaller H3K4me3modi ed region, encode key TFs that regulate embryonic development [29]. It pointed out that promoter modi cation of H3K4me3 and H3K27me3 related to DNA methylation [33] and chromatin compressing [34] to regulate gene transcription.…”

Section: Discussionmentioning

confidence: 99%

The chromatin mapping of H3K4me3 and H3K27me3 modification in ovaries during porcine puberty initiation

Zhong

Yuan

et al. 2020

Preprint

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Background The biological structure and function of mammalian ovaries undergo important developmental changes during pre- puberty. Posttranslational modified histones dynamically regulate ovarian development, which also can respond to the onset of puberty with heritable changes in gene expression that are associated with nucleosome modifications. This research used chromatin immunoprecipitation followed by sequencing (ChIP-seq) technology and bioinformatic analysis to confirm the histone-DNA interaction in pre-puberty ovarian follicles (PreOV) and in-puberty ovarian follicles (InOV). Then, employed qRT-PCR, and cell proliferation and apoptosis testing to further investigate the function of H3K4me3and H3K27me3 in gene transcription and cell growth. Results With the onset of puberty, ChIP-Seq found 946 higher- enrichment and 916 lower- enrichment genes were significantly differentially modified with H3K4me3, while 1954 higher- enrichment and 882 lower- enrichment genes were significantly differentially modified with H3K27me3 in InOV vs. PreOV. Then interestingly, 88 significantly genes were associated with significantly differentially H3K4me3-enriched, H3K4me3-delepted, H3K27me3-enriched, and H3K27me3-delepted modifications, which also were related to female gemmate development pathway, bone mineralization and fatty acid transport, including FOXO3, RUNX1, NOBOX, DMRT1, MYC, LEPTIN, ACVR2, and BMPR1B. Furthermore, compare medium-sized antral with Graff follicles, FOXO3, RUNX1 and BMPR1B were low expressed in medium-sized antral follicles, while NOBOX and LEPTIN were low expressed in Graff follicles. Finally, H3K4me3 exhibited to promote proliferation and anti-apoptosis, whereas H3K27me3 was more to inhibited proliferation and induced cell apoptosis in porcine granulosa cells (pGCs). Conclusions The genome-wide modified profile of H3K4me3 and H3K27me3 showed that H3K27me3 modification was more active than H3K4me3 modification during the onset of puberty in porcine ovaries. H3K4me3 and H3K27me3 acted as activator and repressor to regulate gene transcription that are related to porcine puberty initiation process. Genes including FOXO3, BMPR1B, LEPTIN, RUNX1, involved in networks of female gamete generation pathway associating with ovarian follicle development, ovulation, ovulation cycle process and female gonad development, which showed the further direction to investigate the function of H3K4me3/H3K27me3-targets in puberty initiation.

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“…CpG island methylation in the promoter may be a crucial mechanism regulating gene expression at the epigenetic level (34,35). Moreover, histone modifications alter DNA methylation (36,37). HOTAIR has been found to bind PRC2, mediate H3K27 trimethylation and silence the HOXD locus (38).…”

Section: Discussionmentioning

confidence: 99%

H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR

et al. 2018

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Background: The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) serves as a powerful predictor of tumor progression and overall survival in patients. Our previous studies showed that HOTAIR modulated HOXA1 DNA methylation by reducing DNMT1 and DNMT3b expression in drugresistant small cell lung cancer (SCLC). Moreover, H3 lysine 27 trimethylation (H3K27me3) is catalyzed by enhancer of zeste homolog 2 (EZH2) and plays a critical role in SCLC chemoresistance. However, it is not completely clear whether H3K27me3 affects HOXA1 DNA methylation or whether this effect is mediated by HOTAIR. Methods: The levels of EZH2 and H3K27me3 were identified in SCLC tissues by immunohistochemical (IHC) staining and in SCLC multidrug-resistant cells by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were used to detect and analyze the biological function of H3K27me3. Then, we assessed the role of HOTAIR in the regulation of EZH2 and H3K27me3 by using lentivirus and small interfering RNA. Further, bisulfite sequencing PCR was conducted to detect the methylation levels of HOXA1 DNA. Finally, Western blotting was performed to examine the regulatory role of H3K27me3 in controlling HOTAIR expression in SCLC. Results: In this study, we found that EZH2 and H3K27me3 levels were markedly higher in SCLC tissues and multidrug-resistant SCLC cells. The results indicated that H3K27me3 was related to multidrug resistance. HOTAIR overexpression and knockdown showed that EZH2 and H3K27me3 were regulated by HOTAIR. Moreover, H3K27me3 affected HOXA1 DNA methylation levels. Strikingly, we found that H3K27me3 acted as a negative feedback regulator of HOTAIR. Conclusions: Our study showed that H3K27me3 affects HOXA1 DNA methylation via HOTAIR regulation, indicating that H3K27me3 may be a potential therapy target for SCLC chemoresistance.

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Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection

Cited by 30 publications

References 37 publications

DNA Methylation and Genetic Aberrations in Gastric Cancer

DNA Methylation and Genetic Aberrations in Gastric Cancer

The chromatin mapping of H3K4me3 and H3K27me3 modification in ovaries during porcine puberty initiation

H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR

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