title: A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory.
abstract: The interaction of nuclear pore proteins (Nups) with active genes can promote their transcription. In yeast, some inducible genes interact with the nuclear pore complex both when active and for several generations after being repressed, a phenomenon called epigenetic transcriptional memory. This interaction promotes future reactivation and requires Nup100, a homologue of human Nup98. A similar phenomenon occurs in human cells; for at least four generations after treatment with interferon gamma (IFN-γ), many IFN-γ-inducible genes are induced more rapidly and more strongly than in cells that have not previously been exposed to IFN-γ. In both yeast and human cells, the recently expressed promoters of genes with memory exhibit persistent dimethylation of histone H3 lysine 4 (H3K4me2) and physically interact with Nups and a poised form of RNA polymerase II. However, in human cells, unlike yeast, these interactions occur in the nucleoplasm. In human cells transiently depleted of Nup98 or yeast cells lacking Nup100, transcriptional memory is lost; RNA polymerase II does not remain associated with promoters, H3K4me2 is lost, and the rate of transcriptional reactivation is reduced. These results suggest that Nup100/Nup98 binding to recently expressed promoters plays a conserved role in promoting epigenetic transcriptional memory.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Light
authors.forename: Jonathan
authors.initials: J
authors.lastname: Freaney
authors.forename: Varun
authors.initials: V
authors.lastname: Sood
authors.forename: Abbey
authors.initials: A
authors.lastname: Thompson
authors.forename: Agustina
authors.initials: A
authors.lastname: D'Urso
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
authors.forename: Jason H
authors.initials: JH
authors.lastname: Brickner
mesh_terms: D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D057890:Epigenomics / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; C077731:NUP100 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C093350:nuclear pore complex protein 98; D012319:RNA Polymerase II
references.citation: BMC Bioinformatics. 2009 Feb 03;10:48
references.pmid: 19192299
references.citation: Cell. 2012 Aug 17;150(4):738-51
references.pmid: 22901806
references.citation: PLoS Genet. 2010 Feb 12;6(2):e1000846
references.pmid: 20174442
references.citation: Mol Cell Biol. 2010 Apr;30(8):2046-56
references.pmid: 20123968
references.citation: Mol Cell Biol. 1995 May;15(5):2737-44
references.pmid: 7739554
references.citation: Cell. 2010 Jun 11;141(6):1030-41
references.pmid: 20550937
references.citation: Genes Dev. 2007 Apr 15;21(8):997-1004
references.pmid: 17438002
references.citation: Genes Dev. 2005 May 15;19(10):1188-98
references.pmid: 15905407
references.citation: Genes Dev. 2000 Apr 1;14(7):792-803
references.pmid: 10766736
references.citation: Cell. 2002 May 31;109(5):551-62
references.pmid: 12062099
references.citation: Oncogene. 2001 Sep 10;20(40):5695-707
references.pmid: 11607819
references.citation: Microbes Infect. 2004 Jul;6(8):715-24
references.pmid: 15207818
references.citation: Genes Dev. 2008 Mar 1;22(5):627-39
references.pmid: 18316479
references.citation: Mol Cell. 2005 Apr 15;18(2):171-83
references.pmid: 15837421
references.citation: Cell. 2012 Sep 14;150(6):1158-69
references.pmid: 22959268
references.citation: Cell. 1999 Apr 2;97(1):41-51
references.pmid: 10199401
references.citation: Cell. 2010 Apr 30;141(3):432-45
references.pmid: 20434984
references.citation: Cold Spring Harb Symp Quant Biol. 1998;63:347-56
references.pmid: 10384299
references.citation: Trends Cell Biol. 2003 Dec;13(12):622-8
references.pmid: 14624840
references.citation: PLoS Biol. 2004 Nov;2(11):e342
references.pmid: 15455074
references.citation: Dev Cell. 2003 Jun;4(6):775-89
references.pmid: 12791264
references.citation: Nature. 2007 Nov 29;450(7170):695-701
references.pmid: 18046406
references.citation: Genetics. 2012 Mar;190(3):855-83
references.pmid: 22419078
references.citation: Cancer Treat Res. 1996;84:73-92
references.pmid: 8724626
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13028-33
references.pmid: 9371794
references.citation: Blood. 1999 Jul 15;94(2):741-7
references.pmid: 10397741
references.citation: Cell. 2007 Apr 6;129(1):83-96
references.pmid: 17418788
references.citation: J Cell Sci. 2000 May;113 ( Pt 9):1565-76
references.pmid: 10751148
references.citation: Gene Expr. 1991 May;1(2):149-67
references.pmid: 1820212
references.citation: J Biol Chem. 1992 May 15;267(14):9933-9
references.pmid: 1577824
references.citation: Nature. 2006 Jun 8;441(7094):774-8
references.pmid: 16760983
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5749-54
references.pmid: 15817685
references.citation: Curr Opin Genet Dev. 2011 Apr;21(2):231-5
references.pmid: 21324670
references.citation: Science. 2008 Mar 28;319(5871):1791-2
references.pmid: 18369138
references.citation: Annu Rev Biochem. 2000;69:729-49
references.pmid: 10966474
references.citation: Genes Dev. 2009 Nov 15;23(22):2610-24
references.pmid: 19933151
references.citation: Mol Biol Cell. 2002 Apr;13(4):1282-97
references.pmid: 11950939
references.citation: Mol Cell. 2006 Aug 4;23(3):297-305
references.pmid: 16885020
references.citation: Cell. 1994 Dec 16;79(6):1103-9
references.pmid: 8001136
references.citation: Mol Biol Cell. 2012 Apr;23(7):1367-75
references.pmid: 22323286
references.citation: Mol Cell Biol. 2003 Oct;23(20):7271-84
references.pmid: 14517296
references.citation: Mol Cell Biol. 2008 Jun;28(12):3979-94
references.pmid: 18391020
references.citation: Mol Cell Biol. 2010 May;30(10):2330-40
references.pmid: 20212085
references.citation: Immunity. 2006 Mar;24(3):295-304
references.pmid: 16546098
references.citation: Nat Genet. 1996 Feb;12(2):159-67
references.pmid: 8563754
references.citation: Genes Dev. 2006 Nov 1;20(21):2922-36
references.pmid: 17079683
references.citation: Curr Biol. 2002 Jul 23;12(14):1240-4
references.pmid: 12176335
references.citation: Cell. 2004 May 14;117(4):427-39
references.pmid: 15137937
references.citation: Mol Cell. 2012 Jan 13;45(1):51-63
references.pmid: 22244332
references.citation: EMBO J. 2007 Dec 12;26(24):4956-65
references.pmid: 18034162
references.citation: Mol Cell. 2008 Aug 8;31(3):337-46
references.pmid: 18691966
references.citation: Nat Cell Biol. 2004 Nov;6(11):1114-21
references.pmid: 15502822
references.citation: Mol Cell. 2010 Oct 8;40(1):112-25
references.pmid: 20932479
references.citation: Annu Rev Biochem. 2011;80:613-43
references.pmid: 21495847
references.citation: Genes Dev. 2004 Oct 15;18(20):2437-68
references.pmid: 15489290
references.citation: J Cell Biol. 1999 Mar 22;144(6):1097-112
references.pmid: 10087256
references.citation: Stat Med. 1990 Jul;9(7):811-8
references.pmid: 2218183
references.citation: PLoS Biol. 2007 Apr;5(4):e81
references.pmid: 17373856
references.citation: Curr Opin Genet Dev. 2002 Apr;12(2):198-209
references.pmid: 11893494
references.citation: Nat Genet. 1996 Feb;12(2):154-8
references.pmid: 8563753
references.citation: Cell Cycle. 2010 Dec 15;9(24):4812-7
references.pmid: 21150273
references.citation: Mol Cell. 2006 Mar 17;21(6):811-23
references.pmid: 16543150
references.citation: PLoS Biol. 2010 Jun 22;8(6):e1000401
references.pmid: 20582323
references.citation: Proc Natl Acad Sci U S A. 1987 Nov;84(21):7552-6
references.pmid: 3313397
references.citation: Nat Cell Biol. 2010 Feb;12(2):111-8
references.pmid: 20098417
references.citation: Cancer Res. 1998 Oct 1;58(19):4269-73
references.pmid: 9766650
references.citation: Methods Enzymol. 2010;470:569-80
references.pmid: 20946825
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11370-5
references.pmid: 10500183
references.citation: Nature. 1996 Sep 26;383(6598):357-60
references.pmid: 8848052
references.citation: PLoS One. 2012;7(5):e37554
references.pmid: 22701520
references.citation: Cell. 2010 Nov 12;143(4):540-51
references.pmid: 21074046
references.citation: Mol Genet Genomics. 2011 Feb;285(2):125-49
references.pmid: 21136082
references.citation: Nature. 2012 Jan 18;483(7389):295-301
references.pmid: 22258509
references.citation: Mol Cell Biol. 2000 Jan;20(1):104-12
references.pmid: 10594013
references.citation: Annu Rev Immunol. 1997;15:749-95
references.pmid: 9143706
references.citation: Genes Dev. 2009 Nov 15;23(22):2604-9
references.pmid: 19933150
references.citation: Science. 2000 May 26;288(5470):1418-22
references.pmid: 10827951
references.citation: Genes Dev. 2000 Oct 1;14(19):2452-60
references.pmid: 11018013
references.citation: J Biol Chem. 2002 Aug 9;277(32):28368-71
references.pmid: 12070136
references.citation: Trends Immunol. 2006 Sep;27(9):405-12
references.pmid: 16870508
references.citation: Cell. 2005 Aug 26;122(4):517-27
references.pmid: 16122420
references.citation: Science. 2000 May 19;288(5469):1242-4
references.pmid: 10817999
references.citation: Nature. 2002 Sep 26;419(6905):407-11
references.pmid: 12353038
references.citation: Cell. 2010 Feb 5;140(3):372-83
references.pmid: 20144761
references.citation: Cell. 2010 Feb 5;140(3):360-71
references.pmid: 20144760
references.citation: Genetics. 2012 Oct;192(2):495-505
references.pmid: 22851651
references.citation: Cancer Biol Ther. 2009 Jul;8(13):1204-11
references.pmid: 19729989
references.citation: Trends Mol Med. 2012 Jan;18(1):36-42
references.pmid: 22056243
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14307-10
references.pmid: 11114191
references.citation: Mol Cell Biol. 2007 Jun;27(11):4198-205
references.pmid: 17387147
references.citation: Clin Cancer Res. 2012 Jun 1;18(11):3015-21
references.pmid: 22615451
references.citation: Nature. 1990 Oct 11;347(6293):558-61
references.pmid: 2170850