title: 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.
abstract: Insulin controls transcription to sustain its physiologic effects for the organism to adapt to environmental changes added to genetic predisposition. Nevertheless, insulin-induced transcriptional regulation by epigenetic factors and in defined nuclear territory remains elusive. Here we show that inner nuclear membrane (INM)-integrated caveolin-2 (Cav-2) regulates insulin-response epigenetic activation of Egr-1 and JunB genes at the nuclear periphery. 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.
authors.affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.
authors.forename: Kyuho
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.
authors.forename: Hayeong
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea.
authors.forename: Donghwan
authors.initials: D
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, Division of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Korea ybpak@gnu.ac.kr.
authors.forename: Yunbae
authors.initials: Y
authors.lastname: Pak
mesh_terms: D000818:Animals; D051243:Caveolin 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D034904:Lamin Type A / Q000378:metabolism*; D009685:Nuclear Envelope / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: C495546:Cav2 protein, rat; D051243:Caveolin 2; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D006657:Histones; D007328:Insulin; C581727:JunB protein, human; C494847:LMNA protein, human; D034904:Lamin Type A; D011994:Recombinant Proteins; D014157:Transcription Factors