Insulin-response epigenetic activation of Egr-1 and JunB genes at the nuclear periphery by A-type lamin-associated pY19-Caveolin-2 in the inner nuclear membrane.
Bottom Line: Insulin controls transcription to sustain its physiologic effects for the organism to adapt to environmental changes added to genetic predisposition.INM-targeted pY19-Cav-2 in response to insulin associates specifically with the A-type lamin, disengages the repressed Egr-1 and JunB promoters from lamin A/C through disassembly of H3K9me3, and facilitates assembly of H3K9ac, H3K18ac and H3K27ac by recruitment of GCN5 and p300 and the subsequent enrichment of RNA polymerase II (Pol II) on the promoters at the nuclear periphery.Our findings show that Cav-2 is an epigenetic regulator of histone H3 modifications, and provide novel mechanisms of insulin-response epigenetic activation at the nuclear periphery.
Affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.Show MeSH
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Mentions: To determine in situ nuclear localization of Egr-1 and JunB genes and to test whether the pY19-Cav-2-mediated dissociation of the promoters from lamin A/C (Figure 4) causes relocation of the genes to the nuclear interior, FISH analysis was performed. Egr-1 and JunB genes were located at the nuclear periphery in the basal condition (Figure 5A and B, top panels). Upon insulin stimulation, no nuclear interior localization of the genes was detected and the position of Egr-1 and JunB genes at the nuclear periphery overlapped with the fluorescence signal of INM-targeted Cav-2 from Golgi (6) (Figure 5A and B, bottom panels). These results show that the Egr-1 and JunB genes localize with Cav-2 at the INM after insulin treatment.
Affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.