Histone H3 K27 acetylation marks a potent enhancer element on the adipogenic master regulator gene Pparg2

Abstract

PPARγ2 is expressed almost exclusively in adipose tissue and plays a central role in adipogenesis. Despite intensive studies over the last 2 decades, the mechanism regulating the expression of the Pparg2 gene, especially the role of cis-regulatory elements, is still not completely understood. Here, we report a comprehensive investigation of the enhancer elements within the murine Pparg2 gene. Utilizing the combined techniques of sequence conservation analysis and chromatin marker examination, we identified a potent enhancer element that augmented the expression of a reporter gene under the control of the Pparg2 promoter by 20-fold. This enhancer element was first identified as highly conserved non-coding sequence 10 (CNS10) and was later shown to be enriched with the enhancer marker H3 K27 acetylation. Further studies identified a binding site for p300 as the essential enhancer element in CNS10. Moreover, p300 physically binds to CNS10 and is required for the enhancer activity of CNS10. The depletion of p300 by siRNA resulted in significantly impaired activation of Pparg2 at the early stages of 3T3-L1 adipogenesis. In summary, our study identified a novel enhancer element on the murine Pparg2 gene and suggested a novel mechanism for the regulation of Pparg2 expression by p300 in 3T3-L1 adipogenesis.

mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis

“…5A]. At differentiating day 2, just before Pparγ2 is initially induced, analysis of specific acetylation marks also reveals a marked decrease in H3K27Ac (a key marker of active enhancers during adipogenesis32 ) in Rictor-iKO PBA , Akt1-iKO PBA , and Acly-iKO PBA cell lines [Supplementary Fig. 5B-D].…”

Control of mesenchymal stem cell biology by histone modifications

“…Depletion of CBP/p300 with ribozyme strongly represses the expression of PPARγ-targeted genes and thus attenuates adipogenic differentiation of preadipocytes [115]. Furthermore, studies on the mechanism of p300-mediated histone modification have revealed that p300 binds to Pparg2 promoter and enhancer regions with enhanced H3/H4ac and H3K27ac, respectively [116,117]. GCN5 and PCAF have also been reported to be involved in MSC adipogenic differentiation.…”

Regulation of Thermogenic Adipocyte Differentiation and Adaptive Thermogenesis Through Histone Acetylation

“…Histone acetylation and deacetylation are catalyzed by HATs and HDACs, respectively (39,(41)(42)(43)(44). In general, multiple lysine residues on histones 3 and 4 are acetylated during transcriptional activation (i.e., H3K9, H3K14, H3K18, H3K23, H3K27, H3K56, and H4K5, H4K8, H4K12, H4K16) (40,42,43,(45)(46)(47). During this process, HATs catalyze the transfer of the acetyl group from acetyl-CoA onto FIGURE 1 | The different types of adipocytes, and HATs/HDACs that regulate brown adipogenesis and adaptive thermogenesis.…”