title: A biophysical model for transcription factories.
abstract: Transcription factories are nuclear domains where gene transcription takes place although the molecular basis for their formation and maintenance are unknown. In this study, we explored how the properties of chromatin as a polymer may contribute to the structure of transcription factories. We found that transcriptional active chromatin contains modifications like histone H4 acetylated at Lysine 16 (H4K16ac). Single fibre analysis showed that this modification spans the entire body of the gene. Furthermore, H4K16ac genes cluster in regions up to 500 Kb alternating active and inactive chromatin. The introduction of H4K16ac in chromatin induces stiffness in the chromatin fibre. The result of this change in flexibility is that chromatin could behave like a multi-block copolymer with repetitions of stiff-flexible (active-inactive chromatin) components. Copolymers with such structure self-organize through spontaneous phase separation into microdomains. Consistent with such model H4K16ac chromatin form foci that associates with nascent transcripts. We propose that transcription factories are the result of the spontaneous concentration of H4K16ac chromatin that are in proximity, mainly in cis.
authors: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK. fjiborra@cnb.csci.es.
authors: Ana Z
authors: AZ
authors: Canals-Hamann
authors: Ricardo Pires
authors: RP
authors: das Neves
authors: Joyce E
authors: JE
authors: Reittie
authors: Carlos
authors: C
authors: Iñiguez
authors: Shamit
authors: S
authors: Soneji
authors: Tariq
authors: T
authors: Enver
authors: Veronica J
authors: VJ
authors: Buckle
authors: Francisco J
authors: FJ
authors: Iborra
references: J Biol Chem. 1987 Mar 15;262(8):3452-61
references: 2434502
references: Mol Cells. 2012 Jul;34(1):1-5
references: 22610406
references: Nat Genet. 2002 Jun;31(2):180-3
references: 11992122
references: Nat Genet. 2006 Jul;38(7):835-41
references: 16767102
references: Mol Biol Cell. 2006 Jul;17(7):2910-20
references: 16624866
references: Genes Dev. 2008 Jan 1;22(1):20-5
references: 18172162
references: Mol Cell Biol. 2004 Jan;24(2):741-56
references: 14701746
references: Histochem Cell Biol. 2002 Aug;118(2):95-103
references: 12189513
references: Theor Biol Med Model. 2007 Apr 12;4:15
references: 17430588
references: Nat Rev Mol Cell Biol. 2006 Sep;7(9):657-66
references: 16912715
references: Prog Mol Subcell Biol. 2005;38:183-206
references: 15881896
references: Curr Opin Cell Biol. 2004 Jun;16(3):256-62
references: 15145349
references: J Cell Sci. 2004 Feb 29;117(Pt 6):899-906
references: 14762111
references: Mol Biol Cell. 1998 Jun;9(6):1523-36
references: 9614191
references: EMBO J. 2005 Jan 26;24(2):347-57
references: 15616580
references: Nat Genet. 2006 Nov;38(11):1348-54
references: 17033623
references: Nat Genet. 2008 Jul;40(7):897-903
references: 18552846
references: J Cell Sci. 2006 Sep 15;119(Pt 18):3876-87
references: 16940354
references: Transcription. 2011 Jan-Feb;2(1):41-4
references: 21326910
references: Nature. 1997 Sep 25;389(6649):349-52
references: 9311776
references: PLoS Biol. 2007 Aug;5(8):e192
references: 17622196
references: J Cell Biol. 2007 Jun 18;177(6):957-67
references: 17576795
references: J Cell Biol. 2008 May 19;181(4):615-23
references: 18490511
references: Biophys J. 2006 May 15;90(10):3712-21
references: 16500976
references: Nat Genet. 2004 Oct;36(10):1065-71
references: 15361872
references: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2259-64
references: 19171905
references: J Mol Biol. 2008 Sep 12;381(4):816-25
references: 18653199
references: Chromosome Res. 2005;13(2):135-44
references: 15861303
references: J Cell Biol. 2002 Dec 9;159(5):777-82
references: 12473686
references: PLoS Biol. 2010 Dec 14;8(12):e1000560
references: 21179497
references: Mol Cell Biol. 1996 Aug;16(8):4349-56
references: 8754835
references: J Cell Sci. 1996 Jun;109 ( Pt 6):1427-36
references: 8799830
references: J Cell Sci. 1998 Aug;111 ( Pt 15):2269-82
references: 9664048
references: Science. 2006 Feb 10;311(5762):844-7
references: 16469925