Identification of DNA response elements regulating expression of CCAAT/enhancer-binding protein (C/EBP) β and δ and MAP kinase-interacting kinases during early adipogenesis

Abstract

Given the high and increasing prevalence of obesity and associated disorders, such as type-2 diabetes, it is important to understand the mechanisms that regulate lipid storage and the differentiation of fat cells, a process termed adipogenesis. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, we refine how the induction of two key adipogenic transcription factors, CCAAT/enhancer-binding proteins (C/EBPs) β and δ are regulated during early adipogenesis. We identify, in the gene promoters of Cebpb and Cebpd, the DNA response elements responsible for binding transcription factors that are activated by cAMP or glucocorticoids. We also show that mitogen-activated protein kinase (MAPK)-interacting kinase 2 (MNK2; Mknk2), which plays a distinct role in diet-induced obesity, is induced during early adipogenesis and identify the functional DNA response elements responsible for regulating its expression. Mknk2 expression is maintained in differentiated 3T3-L1 adipocytes and is expressed at high levels across a range of mouse adipose tissue depots. Together, these new insights help to clarify the transcriptional programme of early adipogenesis and identify Mknk2 as one of potentially many genes up-regulated during adipogenesis.

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

“…The activation of glucocorticoid receptor signaling by its ligand, dexamethasone, is known to be involved in the activation of adipogenesis through the up-regulation of proadipogenic transcription factors [255]. Specifically, GR activation was shown to be involved in the up-regulation of C/EBPβ [256,257] and C/EBPδ [258] expression with the subsequent induction of C/EBPα. It has been also demonstrated that GR-induced adipogenesis may be mediated by KLF-15-induced PPARγ activation [259].…”

Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

“…It has been reported that both C/EBPβ and C/EBPδ were involved in the chondrocyte differentiation, heart development and early regulation of fat formation. [55][56][57] The sub-group III includes C/EBPγ and C/ EBPζ genes, which it has been reported that they are important regulators of cellular stress response networks to maintain the basic life activities of cells. 58 Regulation of gene expression is one of the most important and complex issues in biology.…”

Dynamics of Transcription Factors in Three Early Phases of Osteogenic, Adipogenic, and Chondrogenic Differentiation Determining the Fate of Bone Marrow Mesenchymal Stem Cells in Rats

“…Overexpression of RUNX2 in non-osteoblastic cells and adipose-tissue-derived MSCs elevates the level of osteoblastic markers, promotes mineralization and inhibits lineage commitment to adipocytes, indicating that a single TF is important for bone development and osteoblast differentiation ( Robert et al, 2020 ). During adipogenesis, the production of cyclic AMP is augmented, resulting in phosphorylation of CREB and an increased expression of CEBPβ ( Merrett et al, 2020 ). CEBPβ, together with the other two CEBP family members (CEBPα and CEBPδ), was reported to be implicated in adipogenic differentiation ( Chen et al, 2016 ; Hu et al, 2018 ; Robert et al, 2020 ).…”