title: Binding of TFIIIC to sine elements controls the relocation of activity-dependent neuronal genes to transcription factories.
abstract: In neurons, the timely and accurate expression of genes in response to synaptic activity relies on the interplay between epigenetic modifications of histones, recruitment of regulatory proteins to chromatin and changes to nuclear structure. To identify genes and regulatory elements responsive to synaptic activation in vivo, we performed a genome-wide ChIPseq analysis of acetylated histone H3 using somatosensory cortex of mice exposed to novel enriched environmental (NEE) conditions. We discovered that Short Interspersed Elements (SINEs) located distal to promoters of activity-dependent genes became acetylated following exposure to NEE and were bound by the general transcription factor TFIIIC. Importantly, under depolarizing conditions, inducible genes relocated to transcription factories (TFs), and this event was controlled by TFIIIC. Silencing of the TFIIIC subunit Gtf3c5 in non-stimulated neurons induced uncontrolled relocation to TFs and transcription of activity-dependent genes. Remarkably, in cortical neurons, silencing of Gtf3c5 mimicked the effects of chronic depolarization, inducing a dramatic increase of both dendritic length and branching. These findings reveal a novel and essential regulatory function of both SINEs and TFIIIC in mediating gene relocation and transcription. They also suggest that TFIIIC may regulate the rearrangement of nuclear architecture, allowing the coordinated expression of activity-dependent neuronal genes.
authors: MRC Laboratory for Molecular and Cell Biology, University College London, London, United Kingdom.
authors: Luca
authors: L
authors: Crepaldi
authors: Cristina
authors: C
authors: Policarpi
authors: Alessandro
authors: A
authors: Coatti
authors: William T
authors: WT
authors: Sherlock
authors: Bart C
authors: BC
authors: Jongbloets
authors: Thomas A
authors: TA
authors: Down
authors: Antonella
authors: A
authors: Riccio
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D019474:Transcription Factors, TFIII / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000098832:Transcription Factor TFIIIC
chemical_list: D002843:Chromatin; D006657:Histones; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC
references: PLoS Biol. 2007 Aug;5(8):e192
references: 17622196
references: Science. 1993 Apr 9;260(5105):181-6
references: 8097060
references: Mol Cell. 2006 Jan 20;21(2):283-94
references: 16427017
references: Nucleic Acids Res. 2005 Mar 10;33(5):1445-53
references: 15760844
references: Mol Cell. 2002 Dec;10(6):1453-65
references: 12504019
references: Nat Struct Mol Biol. 2010 May;17(5):620-8
references: 20418882
references: Nat Genet. 2007 Dec;39(12):1507-11
references: 17994021
references: J Neurosci. 2010 Jun 9;30(23):7910-6
references: 20534839
references: Science. 1988 Dec 23;242(4886):1687-91
references: 3201257
references: Cell. 2007 Feb 23;128(4):707-19
references: 17320508
references: Science. 1986 Oct 3;234(4772):80-3
references: 3749894
references: Methods. 2002 Jan;26(1):10-8
references: 12054900
references: Nat Genet. 2010 Jan;42(1):53-61
references: 20010836
references: Mol Cell Biol. 2008 Sep;28(18):5764-76
references: 18644873
references: Genome Res. 2009 Oct;19(10):1742-51
references: 19713549
references: Cell. 2009 Sep 4;138(5):1019-31
references: 19698979
references: Nature. 2010 Nov 18;468(7322):443-6
references: 21085180
references: Front Biosci (Landmark Ed). 2012 Jan 01;17:1345-61
references: 22201808
references: Nat Genet. 2008 Jul;40(7):897-903
references: 18552846
references: Cell. 2006 Jun 2;125(5):859-72
references: 16751097
references: Nat Rev Genet. 2009 Jul;10(7):457-66
references: 19506577
references: Cell. 1994 Nov 4;79(3):449-58
references: 7954811
references: Mol Cell Biol. 2004 May;24(10):4118-27
references: 15121834
references: Nat Neurosci. 1999 Dec;2(12):1120-4
references: 10570490
references: Neuron. 1995 Feb;14(2):433-45
references: 7857651
references: Nat Neurosci. 2010 Nov;13(11):1330-7
references: 20975757
references: J Neurosci. 2013 Feb 6;33(6):2507-11
references: 23392678
references: J Neurosci. 2009 Nov 25;29(47):14687-700
references: 19940164
references: Nat Genet. 2004 Oct;36(10):1065-71
references: 15361872
references: Brain Res. 1978 Sep 29;153(3):563-76
references: 698794
references: Nucleic Acids Res. 2000 Mar 15;28(6):1283-98
references: 10684922
references: Nat Rev Neurosci. 2000 Dec;1(3):191-8
references: 11257907
references: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4220-5
references: 18334644
references: Annu Rev Genet. 2008;42:587-617
references: 18680436
references: Nat Rev Mol Cell Biol. 2008 Mar;9(3):206-18
references: 18292778
references: Genes Dev. 2008 Jan 1;22(1):20-5
references: 18172162
references: Neuron. 2002 Jun 13;34(6):999-1010
references: 12086646
references: Nat Rev Mol Cell Biol. 2006 Aug;7(8):557-67
references: 16936696
references: Proc Natl Acad Sci U S A. 1984 May;81(10):3123-7
references: 6587343
references: Nat Rev Mol Cell Biol. 2006 May;7(5):311-22
references: 16633335
references: Nat Neurosci. 2011 May 29;14(7):848-56
references: 21623364
references: Genome Res. 2011 Mar;21(3):422-32
references: 21324874
references: Genes Dev. 2013 Apr 1;27(7):767-77
references: 23592796
references: Nature. 2005 Aug 11;436(7052):876-80
references: 15988478
references: Curr Opin Genet Dev. 2012 Apr;22(2):110-4
references: 22365496
references: Science. 2009 Feb 20;323(5917):1074-7
references: 19119186
references: Science. 2007 Jul 13;317(5835):248-51
references: 17626886
references: Epigenetics Chromatin. 2012 Jan 09;5(1):1
references: 22230046
references: Nature. 2008 Sep 18;455(7211):411-5
references: 18754010
references: Development. 2010 Feb;137(4):579-84
references: 20110323
references: Nat Rev Genet. 2007 Feb;8(2):104-15
references: 17230197
references: J Biol Chem. 2003 Mar 21;278(12):10450-7
references: 12533520
references: Genes Dev. 2008 Aug 15;22(16):2215-27
references: 18708580
references: Annu Rev Neurosci. 2008;31:563-90
references: 18558867
references: Neuroscience. 1999;94(1):279-86
references: 10613518
references: Nat Struct Mol Biol. 2010 May;17(5):635-40
references: 20418883
references: Mol Cell Biol. 1999 Nov;19(11):7697-704
references: 10523658
references: Nat Rev Neurosci. 2006 Sep;7(9):697-709
references: 16924259
references: Nature. 2010 May 13;465(7295):182-7
references: 20393465
references: Genes Dev. 2005 Mar 1;19(5):542-52
references: 15706033
references: Neurosci Lett. 1992 Apr 13;138(1):153-6
references: 1407655
references: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7757-61
references: 2170987
references: Neuron. 2008 Dec 26;60(6):961-74
references: 19109904
references: J Mol Biol. 2010 Jan 8;395(1):1-10
references: 19852969
references: Nature. 2005 Jun 16;435(7044):903-10
references: 15959507
references: J Cell Sci. 1996 Jun;109 ( Pt 6):1427-36
references: 8799830
references: Nucleic Acids Res. 2012 Jan;40(1):270-83
references: 21911356
references: Nat Genet. 2002 Dec;32(4):623-6
references: 12426570
references: Nature. 2008 Oct 30;455(7217):1198-204
references: 18815592
references: Mol Biol Cell. 2012 Jul;23(14):2741-54
references: 22496415
references: Nat Immunol. 2004 Oct;5(10):1017-27
references: 15378057
references: Annu Rev Biochem. 1986;55:631-61
references: 2427017
references: PLoS One. 2011;6(12):e28497
references: 22174821