A Novel Dnmt3a1 Transcript Inhibits Adipogenesis

Bahareldin A Abdalla; Zhenhui Li; Hongjia Ouyang; Endashaw Jebessa; Tianhao Sun; Jia-Ao Yu; Bolin Cai; Biao Chen; Qinghua Nie; Xiquan Zhang

doi:10.3389/fphys.2018.01270

A Novel Dnmt3a1 Transcript Inhibits Adipogenesis

Front Physiol. 2018 Oct 2:9:1270. doi: 10.3389/fphys.2018.01270. eCollection 2018.

Authors

Bahareldin A Abdalla^{1

2

3}, Zhenhui Li^{1

2

3}, Hongjia Ouyang^{1

2

3}, Endashaw Jebessa^{1

2

3}, Tianhao Sun^{1

2

3}, Jia-Ao Yu^{1

2

3}, Bolin Cai^{1

2

3}, Biao Chen^{1

2

3}, Qinghua Nie^{1

2

3}, Xiquan Zhang^{1

2

3}

Affiliations

¹ Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, China.
² National-Local Joint Engineering Research Center for Livestock Breeding, Guangzhou, China.
³ Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, the Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, China.

Abstract

DNA (cytosine-5)-methyltransferase 3a (Dnmt3a) is an enzyme that catalyzes the transfer of methyl groups to specific CpG forms in DNA. In mammals, two variant transcripts of Dnmt3a have been successfully identified. To the best of our knowledge, no Dnmt3a transcripts in an avian have been successfully identified. This study was performed to detect different transcripts of Dnmt3a in chickens and to examine whether a novel Dnmt3a transcript named Dnmt3a1 may regulate adipogenesis. In addition to cloning, sequencing, transcript detection, and expression studies, a novel Dnmt3a1 transcript overexpression and knockdown were conducted to explore the potential role of Dnmt3a1 in preadipocyte proliferation and the early stage of adipocyte differentiation. In chicken abdominal fat tissue, we detected a novel Dnmt3a1 transcript that differs from Dnmt3a by lacking 23 amino acids at the exon-1/exon-2 border. Dnmt3a1 mRNA was ubiquitously expressed in a variety of tissues or cells and highly expressed in chicken adipose tissue/cells. The expression of Dnmt3a1 was regulated under different physiological conditions including aging, fasting, and high-fat diet. In addition, overexpression of Dnmt3a1 significantly decreased preadipocyte proliferation and induced cell-cycle arrest while its inhibition increased cell proliferation and S-phase cells. Furthermore, the overexpression of Dnmt3a1 significantly upregulated the mRNA level of cell-cycle-related genes, such as CDKN1A, CDKN1B, CCNB3, CCND2, CCNG2, CDKN2B, and CDK9, or the protein level of CDKN1A, CDKN1B, and CCNG2. Conversely, the knockdown of Dnmt3a1 by siRNA had the opposite effects. Moreover, during early adipocyte differentiation, the overexpression of Dnmt3a1 significantly decreased the mRNA and the protein levels of PPAR-γ, C/EBP-α, ADIPOR1, and STAT3, and the mRNA levels of FAS, LEPR, LPL, PRKAB2, and ATGL. In contrast, their expression was significantly increased after the knockdown of Dnmt3a1. Taken together, we identified a novel transcript of Dnmt3a, and it played a potential role in adipogenesis.

Keywords: Dnmt3a; Dnmt3a1 transcript; aging; early differentiation; expression; high-fat diet; preadipocytes proliferation.