HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression

Abstract

Obesity and its associated metabolic disease do serious harm to human health. The transcriptional cascade network with transcription factors as the core is the focus of current research on adipogenesis and its mechanism. Previous studies have found that HMG domain protein 20A (HMG20A) is highly expressed in the early stage of adipogenic differentiation of porcine intramuscular fat (IMF), which may be involved in regulating adipogenesis. In this study, HMG20A was found to play a key negative regulatory role in adipogenesis. Gain- and loss-of-function studies revealed that HMG20A inhibited the differentiation of SVF cells and C3H10T1/2 cells into mature adipocytes. RNA-seq was used to screen differentially expressed genes after HMG20A knockdown. qRT-PCR and ChIP-PCR confirmed that MEF2C was the real target of HMG20A, and HMG20A played a negative regulatory role through MEF2C. HMG20A binding protein LSD1 was found to alleviate the inhibitory effect of HMG20A on adipogenesis. Further studies showed that HMG20A could cooperate with LSD1 to increase the H3K4me2 of the MEF2C promoter and then increase the expression of MEF2C. Collectively, these findings highlight a role for HMG20A-dependent transcriptional and epigenetic regulation in adipogenesis.

CircMEF2C(2, 3) modulates proliferation and adipogenesis of porcine intramuscular preadipocytes by miR-383/671-3p/MEF2C axis

“…This regulatory interplay may hold significant implications in the context of adipogenic differentiation. 20 Our study identified a homologous circRNA of MEF2C in porcine intramuscular preadipocytes through a series of experimental procedures. This circRNA originates from exons 2 and 3 of the MEF2C gene, and in line with established nomenclature principles for circRNAs, we designated it as circMEF2C(2, 3).…”

“…Our findings also indicate that MEF2C operates as a downstream target gene of HMG20A and experiences co-regulation by HMG20A and LSD1 , implicating its involvement in adipose generation. 20 Nonetheless, the upstream regulatory mechanisms governing MEF2C remain unexplored. RNA sequencing was performed the expression of circMEF2C(2, 3) decreased in obese-type pig breeds (Mashen) compared with lean-type pig breeds (Large White).…”

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients

“…HMG20A silencing promoted adipogenic differentiation of porcine myogenic stromal vascular fraction (SVF) cells and C3H10T1/2 cells and thus it negatively regulates adipogenesis, hence not likely to promote diabetes. 52 Yet, the pathophysiological consequence of the rs7178572 SNP associated with adipogenesis is still unknown. The SNP rs758747 (C>T) located in NLR family CARD domain containing 3 ( NLRC3 ) gene was also found to be negatively associated with restenosis in diabetic women.…”

Intermuscular adipose tissue in obesity and related disorders: cellular origins, biological characteristics and regulatory mechanisms

“…In addition, Li et al. found that HMG20A exerts inhibitory effects on adipogenesis in porcine muscle SVFs and C3H10T1/2 cells through its interaction with lysine-specific demethylase 1 (LSD1) ( 64 ). Mozzetta et al.…”

“…In addition, Li et al found that HMG20A exerts inhibitory effects on adipogenesis in porcine muscle SVFs and C3H10T1/2 cells through its interaction with lysine-specific demethylase 1 (LSD1) (64). Mozzetta et al found that histone deacetylase inhibitors (HDACis) repressed the adipogenic potential of FAPs and enhanced the myogenic differentiation of SCs in young dystrophic mice but not in old mdx mice (65).…”