title: How to build a yeast nucleus.
abstract: Biological functions including gene expression and DNA repair are affected by the 3D architecture of the genome, but the underlying mechanisms are still unknown. Notably, it remains unclear to what extent nuclear architecture is driven by generic physical properties of polymers or by specific factors such as proteins binding particular DNA sequences. The budding yeast nucleus has been intensely studied by imaging and biochemical techniques, resulting in a large quantitative data set on locus positions and DNA contact frequencies. We recently described a quantitative model of the interphase yeast nucleus in which chromosomes are represented as passively moving polymer chains. This model ignores the DNA sequence information except for specific constraints at the centromeres, telomeres, and the ribosomal DNA (rDNA). Despite its simplicity, the model accounts for a large majority of experimental data, including absolute and relative locus positions and contact frequency patterns at chromosomal and subchromosomal scales. Here, we also illustrate the model's ability to reproduce observed features of chromatin movements. Our results strongly suggest that the dynamic large-scale architecture of the yeast nucleus is dominated by statistical properties of randomly moving polymers with a few sequence-specific constraints, rather than by a large number of DNA-specific factors or epigenetic modifications. In addition, we show that our model accounts for recently measured variations in homologous recombination efficiency, illustrating its potential for quantitatively understanding functional consequences of nuclear architecture.
authors: Institut Pasteur; Unité Imagerie et Modélisation; CNRS URA 2582; Paris, France.
authors: Hua
authors: H
authors: Wong
authors: Jean-Michel
authors: JM
authors: Arbona
authors: Christophe
authors: C
authors: Zimmer
mesh_terms: D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics
chemical_list: D002843:Chromatin
keywords: DNA repair; budding yeast; chromosome conformation capture; chromosome dynamics; chromosome structure; computational model; genome architecture; homologous recombination; nucleolus; polymer physics
references: Science. 2009 Oct 9;326(5950):289-93
references: 19815776
references: Curr Biol. 2002 Dec 23;12(24):2076-89
references: 12498682
references: Int Rev Cell Mol Biol. 2014;307:275-349
references: 24380598
references: Curr Opin Cell Biol. 2011 Jun;23(3):338-45
references: 21292462
references: Nature. 2006 Jun 8;441(7094):774-8
references: 16760983
references: Development. 2005 May;132(9):2215-23
references: 15829525
references: Nucleus. 2012 Jul 1;3(4):370-83
references: 22688649
references: J Cell Biol. 2006 Jan 16;172(2):189-99
references: 16418532
references: Cold Spring Harb Perspect Biol. 2010 Aug;2(8):a000612
references: 20554704
references: Curr Biol. 1997 Dec 1;7(12):930-9
references: 9382846
references: Nat Cell Biol. 2012 Apr 08;14(5):502-9
references: 22484486
references: Nature. 2006 Jun 8;441(7094):770-3
references: 16760982
references: Semin Cancer Biol. 2007 Feb;17(1):80-90
references: 17137790
references: Nature. 1998 Aug 6;394(6693):592-5
references: 9707122
references: PLoS Comput Biol. 2008 Aug 22;4(8):e1000153
references: 18725929
references: J Cell Biol. 2005 Jan 31;168(3):375-87
references: 15684028
references: Biophys J. 2010 Jun 2;98(11):2410-9
references: 20513384
references: Chromosoma. 1999 May;108(2):103-13
references: 10382072
references: J Biol Chem. 2008 Dec 12;283(50):34532-40
references: 18930918
references: Nature. 2010 May 20;465(7296):363-7
references: 20436457
references: Nat Methods. 2008 Dec;5(12):1031-7
references: 18978785
references: Nat Biotechnol. 2011 Nov 20;29(12):1109-13
references: 22101486
references: Nat Cell Biol. 2012 Apr 08;14(5):510-7
references: 22484485
references: Fungal Genet Biol. 2009 Nov;46(11):879-86
references: 19628047
references: Nat Genet. 2004 Oct;36(10):1065-71
references: 15361872
references: Nat Rev Mol Cell Biol. 2010 May;11(5):317-28
references: 20414256
references: J Cell Biol. 2011 Mar 7;192(5):723-33
references: 21383075
references: Mol Cell Biol. 2008 Jul;28(14):4576-87
references: 18474615
references: Nat Rev Genet. 2001 Apr;2(4):292-301
references: 11283701
references: Genes Dev. 2012 Feb 15;26(4):369-83
references: 22345518
references: J Cell Biol. 2013 Jul 22;202(2):201-10
references: 23878273
references: Curr Biol. 2012 Oct 23;22(20):1881-90
references: 22940469
references: Biophys J. 2012 Jan 18;102(2):296-304
references: 22339866
references: Nucleus. 2012 Sep-Oct;3(5):404-10
references: 22825571
references: Mol Plant. 2010 Jul;3(4):678-90
references: 20601371
references: J Cell Sci. 2000 Jun;113 ( Pt 11):1903-12
references: 10806101
references: Curr Opin Cell Biol. 2007 Jun;19(3):305-10
references: 17467257
references: Genome Res. 2012 Jul;22(7):1295-305
references: 22619363
references: Nat Rev Genet. 2008 Jan;9(1):27-37
references: 18040271
references: Nat Cell Biol. 2013 Jun;15(6):694-9
references: 23644470
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2025-30
references: 20080699
references: Science. 2001 Dec 7;294(5549):2181-6
references: 11739961