AUTHOR=Abdalla Bahareldin A. , Li Zhenhui , Ouyang Hongjia , Jebessa Endashaw , Sun Tianhao , Yu Jia-ao , Cai Bolin , Chen Biao , Nie Qinghua , Zhang Xiquan 

TITLE=A Novel Dnmt3a1 Transcript Inhibits Adipogenesis

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01270

DOI=10.3389/fphys.2018.01270

ISSN=1664-042X

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