Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Zhang, Lianjiang; Liu, Siyuan; Zhu, Yunhui; Gao, Yan; Chen, Jian; Yuan, Bao; Jiang, Hao; Dai, Li-Shang; Zhang, Jiabao

doi:10.1159/000447805

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Moreover, TET-dependent 5mC oxidation has been implicated in the modulation of enhancer activity during differentiation 25,26 . Importantly, TDG is required for proper neuronal differentiation in vitro 27 and, according to a recent report, its knockdown affects differentiation of pig preadipocytes 28 . Furthermore, TDG knockout embryos die at 11.5 dpc, the developmental stage of active organogenesis when differentiation of various types of cellular progenitors is underway 27,29 .…”

Section: Discussionmentioning

confidence: 99%

Dynamics of 5-carboxylcytosine during hepatic differentiation: Potential general role for active demethylation by DNA repair in lineage specification

Lewis

Foster

et al. 2017

Epigenetics

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Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operational in this system; however, it is still unknown if TDG/BER-dependent demethylation is used during other types of cellular differentiation. Here we analyze dynamics of the global levels of 5hmC and 5caC during differentiation of human pluripotent stem cells toward hepatic endoderm. We show that, similar to differentiating NSCs, 5caC transiently accumulates during hepatic differentiation. The levels of 5caC increase during specification of foregut, peak at the stage of hepatic endoderm commitment, and drop in differentiating cells concurrently with the onset of expression of α fetoprotein, a marker of committed hepatic progenitors. Moreover, we show that 5caC accumulates at promoter regions of several genes expressed during hepatic specification at differentiation stages corresponding to the beginning of their expression. Our data indicate that transient 5caC accumulation is a common feature of 2 different types (neural/glial and endoderm/hepatic) of cellular differentiation. This suggests that oxidation of 5mC may represent a general mechanism of rearrangement of 5mC profiles during lineage specification of somatic cells in mammals.

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Section: Discussionmentioning

confidence: 99%

Dynamics of 5-carboxylcytosine during hepatic differentiation: Potential general role for active demethylation by DNA repair in lineage specification

Lewis

Foster

et al. 2017

Epigenetics

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C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

Lu¹,

Du²,

Yao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. Methods: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. Results: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial–mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

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Thymine DNA Glycosylase Gene Knockdown Can Affect the Differentiation of Pig Preadipocytes

Cited by 2 publications

References 26 publications

Dynamics of 5-carboxylcytosine during hepatic differentiation: Potential general role for active demethylation by DNA repair in lineage specification

Dynamics of 5-carboxylcytosine during hepatic differentiation: Potential general role for active demethylation by DNA repair in lineage specification

C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting β-Catenin

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