Functional regulation of hypoxia inducible factor-1α by SET9 lysine methyltransferase

Liu, Qiong; Geng, Hao; Xue, Changhui; Beer, Tomasz M.; Qian, David Z.

doi:10.1016/j.bbamcr.2015.01.011

Cited by 27 publications

(24 citation statements)

References 48 publications

(56 reference statements)

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“…1B, HIF1A-AS1 was complementary upon 117 nt to the HIF-1α mRNA 5'UTR (HIF1A-AS1: 117 to 1, HIF-1α mRNA: 307 to 423), while HIF1A-AS2 was complementary upon 1,221 nt to HIF-1α mRNA 3'UTR (HIF1A-AS2: 2,051 to 831, HIF-1α mRNA: 2,839 to 4,059). consensus putative HRE sequence was 5'-(A/G)GTG-3', which has been identified in many hypoxia-inducible genes, such as VEGF and EPO (24,25). commonly, the promoter region was from -2,000 to +200 bp from the RNA transcription initiation site.…”

Section: Resultsmentioning

confidence: 99%

Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia

Chen

Liu

et al. 2017

International Journal of Molecular Medicine

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Hypoxia‑inducible factor‑1α (HIF‑1α) is essential for regulating the osteogenic differentiation of periodontal ligament cells (PDLCs). The regulatory mechanism of HIF‑1α transcription is still not clear. Recently, two long non‑coding RNAs, HIF1A antisense RNA 1 (HIF1A‑AS1) and HIF1A antisense RNA 2 (HIF1A‑AS2), were found to regulate HIF‑1α mRNA, but the regulatory mechanisms among HIF‑1α, HIF1A‑AS1 and HIF1A‑AS2 have not been well studied. We hypothesized that HIF1A‑AS1 and HIF1A‑AS2 play important roles in the osteogenic differentiation of PDLCs by regulating HIF‑1α. In the present study, we showed that expression levels of HIF1A‑AS1, HIF1A‑AS2, HIF‑1α and osteogenic biomarkers were time‑dependent under hypoxia. Even though both HIF1A‑AS1 and HIF1A‑AS2 were complementary to HIF‑1α mRNA, only HIF1A‑AS2 showed an inhibitory effect on HIF‑1α in PDLCs. Moreover, HIF‑1α had positive regulatory effects on HIF1A‑AS1 and HIF1A‑AS2. HIF‑1α promoted the osteogenic differentiation of PDLCs, and HIF1A‑AS2 had a negative effect on the osteogenic differentiation of PDLCs. Altogether, the present study revealed the complex relationships among HIF1A‑AS1, HIF1A‑AS2 and HIF‑1α, as well as their roles in regulating the osteogenic differentiation of PDLCs. These findings provide a theoretical basis for promoting periodontal tissue regeneration and repair during orthodontic tooth movement.

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Section: Resultsmentioning

confidence: 99%

Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia

Chen

Liu

et al. 2017

International Journal of Molecular Medicine

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“…SETD7 (also known as SET7, SET9 and SET7/9), a SET domain containing lysine methyltransferase 7, specifically monomethylates lysine 4 at histone 3 (H3K4me1) and activates its involved genes expression [ 1 ]. Additionally, SETD7 has also been discovered to monomethylate a series of non-histone proteins, such as p53 [ 2 ], DNA cytosine methyltransferase 1 (DNMT1) [ 3 ], E2 promoter-binding factor 1 (E2F1) [ 4 , 5 ], hypoxia-inducible factor 1α (HIF1α) [ 6 , 7 ], YAP [ 8 ] and NF-κb [ 9 ]. These methylations lead to various and even contradictory results.…”

Section: Introductionmentioning

confidence: 99%

SETD7 is a prognosis predicting factor of breast cancer and regulates redox homeostasis

Huang

et al. 2017

Oncotarget

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SETD7 is a methyltransferase that specifically catalyzes the monomethylation of lysine 4 on histone H3. A variety of studies has revealed the role of SETD7 in posttranslational modifications of non-histone proteins. However, the prognostic value of SETD7 on breast cancer and the ability of SETD7 of regulating intrinsic redox homeostasis has never been investigated. In this study, using The Cancer Genome Atlas (TCGA) database, we revealed that SETD7 was a potential prognostic marker of breast cancer. Median survival time of patients with low SETD7 expression (18.1 years) was twice than that of SETD7 low-expressed patients (9.5 years). We demonstrated that SETD7 promoted tumor cell proliferation and prevented cell apoptosis and that SETD7 delicately maintained the redox homeostasis through regulating the levels of GSH/GSSG and ROS. Further studies indicated that SETD7 was a positive activator of KEAP1-NRF2 pathway. Using dual luciferase assay, we revealed the role of SETD7 as a transcriptional activator of antioxidant enzymes. Downregulation of SETD7 in MCF7 and MDA-MB-231 cells impaired the expression of antioxidant enzymes and induces imbalance of redox status. Together, we proposed SETD7 as a prognostic marker of breast cancer and a novel antioxidant promoter under oxidative stress in breast cancer.

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“…SETD7 was suggested as a good candidate for drug targeting because it is the enzyme that methylates AR in PCa [17]. This might reflect close involvement of SETD7 in tumorigenesis by regulating methylation of various cellular targets, including RORα2 in PCa [34][35][36]. It is, therefore, tempting to explore the possibility that malignant progression of PCa cells might prefer methylated RORα2, utilizing either hyperactivation of SETD7 or, conversely, inactivation of JHDM3A [37,38].…”

Section: Discussionmentioning

confidence: 99%

Isoform-Specific Lysine Methylation of RORα2 by SETD7 Is Required for Association of the TIP60 Coactivator Complex in Prostate Cancer Progression

Song

Chu

Park

et al. 2020

IJMS

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The retinoid acid-related orphan receptor α (RORα), a member of the orphan nuclear receptor superfamily, functions as an unknown ligand-dependent transcription factor. RORα was shown to regulate a broad array of physiological processes such as Purkinje cell development in the cerebellum, circadian rhythm, lipid and bone metabolism, inhibition of inflammation, and anti-apoptosis. The human RORα gene encodes at least four distinct isoforms (RORα1, -2, -3, -4), which differ only in their N-terminal domain (NTD). Two isoforms, RORα2 and 3, are not expressed in mice, whereas RORα1 and 4 are expressed both in mice and humans. In the present study, we identified the specific NTD of RORα2 that enhances prostate tumor progression and proliferation via lysine methylation-mediated recruitment of coactivator complex pontin/Tip60. Upregulation of the RORα2 isoform in prostate cancers putatively promotes tumor formation and progression. Furthermore, binding between coactivator complex and RORα2 is increased by lysine methylation of RORα2 because methylation permits subsequent interaction with binding partners. This methylation-dependent activation is performed by SET domain containing 7 (SETD7) methyltransferase, inducing the oncogenic potential of RORα2. Thus, post-translational lysine methylation of RORα2 modulates oncogenic function of RORα2 in prostate cancer. Exploration of the post-translational modifications of RORα2 provides new avenues for the development of tumor-suppressive therapeutic agents through modulating the human isoform-specific tumorigenic role of RORα2.

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Functional regulation of hypoxia inducible factor-1α by SET9 lysine methyltransferase

Cited by 27 publications

References 48 publications

Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia

Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia

SETD7 is a prognosis predicting factor of breast cancer and regulates redox homeostasis

Isoform-Specific Lysine Methylation of RORα2 by SETD7 Is Required for Association of the TIP60 Coactivator Complex in Prostate Cancer Progression

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