CCNG2
Cyclin-G2
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[i]DNA (cytosine-5)-methyltransferase 3a[/i] ([i]Dnmt3a[/i]) is an enzyme that catalyzes the transfer of methyl groups to specific CpG forms in DNA. In mammals, two variant transcripts of [i]Dnmt3a[/i] have been successfully identified. To the best of our knowledge, no [i]Dnmt3a[/i] transcripts in an avian have been successfully identified. This study was performed to detect different transcripts of [i]Dnmt3a[/i] in chickens and to examine whether a novel [i]Dnmt3a[/i] transcript named [i]Dnmt3a1[/i] may regulate adipogenesis. In addition to cloning, sequencing, transcript detection, and expression studies, a novel [i]Dnmt3a1[/i] transcript overexpression and knockdown were conducted to explore the potential role of [i]Dnmt3a1[/i] in preadipocyte proliferation and the early stage of adipocyte differentiation. In chicken abdominal fat tissue, we detected a novel [i]Dnmt3a1[/i] transcript that differs from [i]Dnmt3a[/i] by lacking 23 amino acids at the exon-1/exon-2 border. [i]Dnmt3a1[/i] mRNA was ubiquitously expressed in a variety of tissues or cells and highly expressed in chicken adipose tissue/cells. The expression of [i]Dnmt3a1[/i] was regulated under different physiological conditions including aging, fasting, and high-fat diet. In addition, overexpression of [i]Dnmt3a1[/i] significantly decreased preadipocyte proliferation and induced cell-cycle arrest while its inhibition increased cell proliferation and S-phase cells. Furthermore, the overexpression of [i]Dnmt3a1[/i] significantly upregulated the mRNA level of cell-cycle-related genes, such as [i]CDKN1A[/i], [i]CDKN1B[/i], [i]CCNB3[/i], [i]CCND2[/i], [i]CCNG2[/i], [i]CDKN2B[/i], and [i]CDK9[/i], or the protein level of CDKN1A, CDKN1B, and CCNG2. Conversely, the knockdown of [i]Dnmt3a1[/i] by siRNA had the opposite effects. Moreover, during early adipocyte differentiation, the overexpression of [i]Dnmt3a1[/i] significantly decreased the mRNA and the protein levels of PPAR-γ, C/EBP-α, ADIPOR1, and STAT3, and the mRNA levels of [i]FAS[/i], [i]LEPR[/i], [i]LPL[/i], [i]PRKAB2[/i], and [i]ATGL.[/i] In contrast, their expression was significantly increased after the knockdown of [i]Dnmt3a1[/i]. Taken together, we identified a novel transcript of [i]Dnmt3a[/i], and it played a potential role in adipogenesis.
Keywords
- Dnmt3a
- Dnmt3a1 transcript
- aging
- early differentiation
- expression
- high-fat diet
- preadipocytes proliferation
Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging. Beyond these transcription factor alterations, analysis of patterns of gene expression involved in hypoxic changes in tissues showed specific increases in metabolic pathway hypoxia-inducible genes, whereas angiogenesis pathway gene changes were more variable in healthy aging tissues across the animals. With periodontitis, aging tissues showed decreases in metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1, TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up-regulation of transcription genes and cellular proliferation genes (FOS, EGR1, MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of these results are related to the epidemiological findings of increased susceptibility and expression of periodontitis with aging. More specifically the findings describe that hypoxic stress may exist in aging gingival tissues before documentation of clinical changes of periodontitis and, so, may provide an explanatory molecular risk factor for an elevated capacity of the tissues to express destructive processes in response to changes in the microbial biofilms characteristic of a more pathogenic microbial challenge.
MeSH Terms
- Age Factors
- Aging
- Animals
- Basic Helix-Loop-Helix Transcription Factors
- Gene Expression
- Hypoxia
- Hypoxia-Inducible Factor 1, alpha Subunit
- Macaca mulatta
- Mucous Membrane
- Periodontitis
- Signal Transduction
Keywords
- aging
- hypoxia
- mucosal tissues
- non-human primates
- periodontitis