The <i>Telomerase Reverse Transcriptase</i> (<i>hTERT</i>) Gene Is a Direct Target of the Histone Methyltransferase SMYD3

Liu, Cheng; Fang, Xiaolei; Ge, Zheng; Jalink, Marit; Kyo, Satoru; Björkholm, Magnus; Gruber, Astrid; Sjøberg, Jan; Xu, Dawei

doi:10.1158/0008-5472.can-06-4126

Cited by 100 publications

(97 citation statements)

References 34 publications

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“…And suppression of hTERT expression also results in elevated p53 and p21 transcription [78]. (c) The histone methyltransferase (SMYD3) implicated in oncogenesis directly transactivates the hTERT promoter and is required for inducible and constitutive hTERT expression in normal and malignant human cells [79]. On the other hand, it has been shown that expression of hTERT up-regulated transcription and promoter activity of DNA 5-methylcytosine transferase I gene (DNMT1) in normal human fibroblasts [73], although the mechanism by which hTERT-induced DNMT1 expression has yet to be determined.…”

Section: Telomerase In the Regulation Of Gene Expressionmentioning

confidence: 99%

Actions of human telomerase beyond telomeres

Cong

Shay²

2008

Cell Res

206

164

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Section: Telomerase In the Regulation Of Gene Expressionmentioning

confidence: 99%

Actions of human telomerase beyond telomeres

Cong

Shay²

2008

Cell Res

206

164

View full text Add to dashboard Cite

“…SMYD3 methylates both H3K4 and H4K5 (Hamamoto et al 2004, Van Aller et al 2012, recruits RNA polymerase II through an RNA helicase to form a transcription complex, and elicits its oncogenic effects by activating the transcription of downstream target genes (Hamamoto et al 2004, 2006, Liu et al 2007. SMYD3 is also involved in apoptosis and the inhibition of cell growth, migration, and invasion (Xu et al 2006, Zou et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…SMYD3 has been reported to be capable of methylating both H3K4 and H4K5 (Hamamoto et al 2004, Van Aller et al 2012. Evidence has accumulated that suggests that SMYD3 recruits RNA polymerase II through an RNA helicase to form a transcription complex and that it elicits its oncogenic effects by activating the transcription of downstream target genes (Hamamoto et al 2004, 2006, Liu et al 2007. Previous reports have demonstrated that enhanced expression of SMYD3 is essential for the growth of human cancer cells (Hamamoto et al 2004(Hamamoto et al , 2006, whereas the suppression of SMYD3 expression leads to apoptosis and the inhibition of cell growth, migration, and invasion (Chen et al 2007, Zou et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Suzuki¹,

Nozawa²,

Tsukamoto³

et al. 2015

Reproduction

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SET and MYND domain-containing protein 3 (Smyd3) is a histone H3 lysine 4 (H3K4) di-and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and activates the transcription of oncogenes and cell cycle genes in human cancer cells. However, the study of Smyd3 in mammalian early embryonic development has not yet been addressed. In the present study, we investigated the expression pattern of Smyd3 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Smyd3 repression on the development of mouse embryos. We showed that Smyd3 mRNA levels increased after the two-cell stage, peaked at the four-cell stage, and gradually decreased thereafter. Moreover, in two-cell to eight-cell embryos, SMYD3 staining was more intense in the nuclei than it was in the cytoplasm. In Smyd3-knockdown embryos, the percentage of inner cell mass (ICM)-derived colony formation and trophectoderm (TE)-derived cell attachment were significantly decreased, which resulted in a reduction in the number of viable offspring. Furthermore, the expression of Oct4 and Cdx2 during mid-preimplantation gene activation was significantly decreased in Smyd3-knockdown embryos. In addition, the transcription levels of ICM and epiblast markers, such as Oct4, Nanog, and Sox2, the transcription levels of primitive endoderm markers, such as Gata6, and the transcription levels of TE markers, such as Cdx2 and Eomes, were significantly decreased in Smyd3-knockdown blastocysts. These findings indicate that SMYD3 plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes.Reproduction (2015) 150 21-30

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“…ChIP assay was carried out as described previously (44,45). The cells with different treatments were cross-linked by incubating them in 1% (vol/vol) formaldehyde-containing medium for 10 min at 37jC and then sonicated to make soluble chromatin with DNA fragments between 200 and 1,000 bp.…”

Section: Chipmentioning

confidence: 99%

“…44, 45): 5 ¶-CCAGGCCGGGCTCCCAGTG-GAT-3 ¶ (forward) and 5 ¶-GGCTTCCCACGTGCGCAGCAG-GA-3 ¶ (reverse); and upstream (hTERT-b) regions: 5 ¶-TCCCC-TTCACGTCCGGCATT-3 ¶ (forward) and 5 ¶-CGTCT-GTGCCCGCGAATCCA-3 ¶ (reverse). The primers for glyceraldehyde-3-phosphate dehydrogenase were described elsewhere (44,45).…”

Section: Chipmentioning

confidence: 99%

The Opposing Effect of Hypoxia-Inducible Factor-2α on Expression of Telomerase Reverse Transcriptase

Lou¹,

Chen

Jalink

et al. 2007

Molecular Cancer Research

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Hypoxia-inducible factor-1A (HIF-1A) has been implicated in the transcriptional regulation of the telomerase reverse transcriptase (hTERT) gene expression and telomerase activity, essential elements for cellular immortalization and transformation. However, controversial results were obtained in different studies. Moreover, it is totally unclear whether HIF-2A, the paralog of HIF-1A, plays a role in regulating hTERT expression. In the present study, we found that hypoxic treatment enhanced hTERT mRNA expression and telomerase activity in three renal cell carcinoma (RCC) cell lines with different genetic backgrounds. Both HIF-1A and HIF-2A were capable of significantly increasing the hTERT promoter activity in these cells. Moreover, depleting HIF-2A led to a down-regulation of hTERT mRNA level in RCC A498 cells expressing constitutive HIF-2A. It was found that HIF-2A bound to the hTERT proximal promoter and enhanced the recruitment of the histone acetyltransferase p300 and histone H3 acetylation locally in A498 cells treated with hypoxia. Increased levels of hTERT mRNA were observed in two of three hypoxia-treated malignant glioma cell lines. However, HIF-1A stimulated whereas HIF-2A inhibited the hTERT promoter activity in these glioma cell lines. Ectopic expression of HIF-2A resulted in diminished hTERT expression in glioma cells. Collectively, HIF-1A activates hTERT and telomerase expression in both RCC and glioma cells, and HIF-2A enhances hTERT expression in RCC cells, whereas it represses the hTERT transcription in glioma cells.

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The Telomerase Reverse Transcriptase (hTERT) Gene Is a Direct Target of the Histone Methyltransferase SMYD3

Cited by 100 publications

References 34 publications

Actions of human telomerase beyond telomeres

Actions of human telomerase beyond telomeres

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

The Opposing Effect of Hypoxia-Inducible Factor-2α on Expression of Telomerase Reverse Transcriptase

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