AUTHOR=Abdalla Bahareldin Ali , Li Zhenhui , Nie Qinghua 

TITLE=A Novel DNA Methyltransferase Dnmt3a3 Splice Variant Represses Preadipocyte Proliferation and Differentiation

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00115

DOI=10.3389/fgene.2020.00115

ISSN=1664-8021

ABSTRACT=<p>Proliferation and differentiation of preadipocyte are essential for the formation of fat tissues. However, the genes that regulate the early stage of preadipocyte differentiation in chicken have remained elusive. Here we identify a novel spliced variant of the DNA methyltransferase <italic>Dnmt3a</italic> gene, named <italic>Dnmt3a3</italic>, that controls early preadipocyte differentiation. <italic>Dnmt3a3</italic> expression is increased at the onset of preadipocyte differentiation and remains elevated during differentiation. Overexpression of <italic>Dnmt3a3</italic> in preadipocytes markedly inhibits proliferation and cell-cycle progression, and this is accompanied by inhibition of the mRNA and protein level of cell-cycle control genes, such as p21 and p27. In addition, forced expression of <italic>Dnmt3a3</italic> in differentiating preadipocytes represses early preadipocyte differentiation, and this was found to be accompanied by inhibition of the mRNA expression levels of early preadipocyte differentiation markers, such as <italic>GATA2</italic>, <italic>GATA3</italic>, <italic>C/EBPα</italic>, <italic>C/EBPβ</italic>, <italic>AP2</italic>, and <italic>PPARγ</italic>, or the protein levels of GATA3, C/EBP<italic>β</italic>, and PPAR<italic>γ</italic>. Taken together, these data demonstrate the participation of <italic>Dnmt3a3</italic> in the proliferation and differentiation process of chicken primary preadipocyte cells.</p>