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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.

Jeong K, Kwon H, Lee J, Jang D, Pak Y - Nucleic Acids Res. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.

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Egr-1 and JunB genes are positioned at nuclear periphery and co-localize with the INM-targeted Cav-2 in response to insulin. The in situ localization of Egr-1 and JunB genes at the nuclear periphery was determined by FISH in Hirc-B cells treated with or without 100 nM insulin for 30 min. Representative images of single confocal sections of nuclei show the immunostained Cav-2 (green), FISH signal (red) and DAPI (blue). The arrows in the merge panel indicate the positive signals in the Alexa Fluor 594-labeled Egr-1 (A) and JunB (B) specific DNA probes. The images on the right show magnifications of the areas framed in the merge images. Scale bars, 20 μm.
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Figure 5: Egr-1 and JunB genes are positioned at nuclear periphery and co-localize with the INM-targeted Cav-2 in response to insulin. The in situ localization of Egr-1 and JunB genes at the nuclear periphery was determined by FISH in Hirc-B cells treated with or without 100 nM insulin for 30 min. Representative images of single confocal sections of nuclei show the immunostained Cav-2 (green), FISH signal (red) and DAPI (blue). The arrows in the merge panel indicate the positive signals in the Alexa Fluor 594-labeled Egr-1 (A) and JunB (B) specific DNA probes. The images on the right show magnifications of the areas framed in the merge images. Scale bars, 20 μm.

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.


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.

Jeong K, Kwon H, Lee J, Jang D, Pak Y - Nucleic Acids Res. (2015)

Egr-1 and JunB genes are positioned at nuclear periphery and co-localize with the INM-targeted Cav-2 in response to insulin. The in situ localization of Egr-1 and JunB genes at the nuclear periphery was determined by FISH in Hirc-B cells treated with or without 100 nM insulin for 30 min. Representative images of single confocal sections of nuclei show the immunostained Cav-2 (green), FISH signal (red) and DAPI (blue). The arrows in the merge panel indicate the positive signals in the Alexa Fluor 594-labeled Egr-1 (A) and JunB (B) specific DNA probes. The images on the right show magnifications of the areas framed in the merge images. Scale bars, 20 μm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4381080&req=5

Figure 5: Egr-1 and JunB genes are positioned at nuclear periphery and co-localize with the INM-targeted Cav-2 in response to insulin. The in situ localization of Egr-1 and JunB genes at the nuclear periphery was determined by FISH in Hirc-B cells treated with or without 100 nM insulin for 30 min. Representative images of single confocal sections of nuclei show the immunostained Cav-2 (green), FISH signal (red) and DAPI (blue). The arrows in the merge panel indicate the positive signals in the Alexa Fluor 594-labeled Egr-1 (A) and JunB (B) specific DNA probes. The images on the right show magnifications of the areas framed in the merge images. Scale bars, 20 μm.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.

Show MeSH
Related in: MedlinePlus