Abstract
Gene expression in higher eukaryotes demands a highly orchestrated series of events that is regulated at many levels. This hierarchical control begins in the nucleus where gene expression is activated by gene transcription. The control of transcription itself is multi-layered and incorporates both genetic and epigenetic features. Epigenetic regulation involves post-translational modification of histones and other chromatin proteins, which define the local chromatin environment of a gene and organizational features, which define the nuclear environment. In this essay, I explore how the nuclear environment can contribute to the regulation of gene expression. I discuss very recent experiments that provide compelling evidence for the widespread formation of gene expression networks during the induction of gene expression and evaluate how the dynamic behaviour of chromatin, which is required during the formation of such networks, fits with present models of nuclear organization.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ashall L, Horton CA, Nelson DE et al (2009) Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription. Science 324:242–246
Baxter J, Merkenschlager M, Fisher AG (2002) Nuclear organization and gene expression. Curr Opin Cell Biol 14:372–376
Berezney R, Mortillaro MJ, Ma H et al (1996) The nuclear matrix: a structural milieu for genomic function. Int Rev Cytol 162A:1–65
Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412
Bernstein BE, Meissner A, Lander ES (2007) The mammalian epigenome. Cell 128:669–681
Brown JM, Green J, Das Neves RP et al (2008) Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 182:1083–1097
Cao K, Capell BC, Erdos MR et al (2007) A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci U S A 104:4949–4954
Conradie R, Bruggeman FJ, Ciliberto A et al (2010) Restriction point control of the mammalian cell cycle via the cyclin E/Cdk2:p27 complex. FEBS J 277:357–367
Cook PR (1999) The organization of replication and transcription. Science 284:1790–1795
Cook PR (2010) A model for all genomes: the role of transcription factories. J Mol Biol 395:1–10
Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301
Dauer WT, Worman HJ (2009) The nuclear envelope as a signaling node in development and disease. Dev Cell 17:626–638
Dechat T, Pfleghaar K, Sengupta K et al (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832–853
de Lanerolle P, Johnson T, Hofmann WA (2005) Actin and myosin I in the nucleus: what next? Nat Struct Mol Biol 12:742–746
Ding SL, Shen CY (2008) Model of human aging: recent findings on Werner’s and Hutchinson-Gilford progeria syndromes. Clin Interv Aging 3:431–444
Dundr M, Ospina JK, Sung MH et al (2007) Actin-dependent intranuclear repositioning of an active gene locus in vivo. J Cell Biol 179:095–103
Emerson BM (2002) Specificity of gene regulation. Cell 109:267–270
Eskiw CH, Rapp A, Carter DR, Cook PR (2008) RNA polymerase II activity is located on the surface of protein-rich transcription factories. J Cell Sci 121:1999–2007
Ferrai C, Xie SQ, Luraghi P et al (2010) Poised transcription factories prime silent uPA gene prior to activation. PLoS Biol 8:e1000270
Filipski E, Lévi F (2009) Circadian disruption in experimental cancer processes. Integr Cancer Ther 8:298–302
Fraser P, Bickmore W (2007) Nuclear organization of the genome and the potential for gene regulation. Nature 447:413–417
Geva-Zatorsky N, Rosenfeld N, Itzkovitz S et al (2006) Oscillations and variability in the p53 system. Mol Syst Biol 2:0033
Goetze S, Mateos-Langerak J, Gierman HJ et al (2007) The three-dimensional structure of human interphase chromosomes in related to the transcriptome map. Mol Cell Biol 27:4475–4487
Gruenbaum Y, Goldman RD, Meyuhas R et al (2003) The nuclear lamina and its functions in the nucleus. Int Rev Cytol 226:1–62
Guelen L, Pagie L, Brasset E et al (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951
Hadjur S, Williams L, Ryan M et al (2009) Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature 460:410–413
Hager GL, McNally JG, Misteli T (2009) Transcription dynamics. Mol Cell 35:741–753
Hu Q, Kwon YS, Nunez E et al (2008) Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc Natl Acad Sci U S A 105:19199–19204
Jackson DA, Hassan AB, Errington RJ et al (1993) Visualization of focal sites of transcription within human nuclei. EMBO J 12:1059–1065
Jackson DA, Iborra FJ, Manders EM et al (1998) Numbers and organization of RNA polymerases, nascent transcripts, and transcription units in HeLa nuclei. Mol Biol Cell 9:1523–1536
Jackson DA, Pombo A (1998) Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J Cell Biol 140:1285–1295
Ko CH, Takahashi JS (2006) Molecular components of the mammalian circadian clock. Hum Mol Genet 15:R271–277
Lamond AI, Spector DL (2003) Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4:605–612
Lanctôt C, Cheutin T, Cremer M et al (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8:104–115
Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293
Maniatis T, Reed R (2002) An extensive network of coupling among gene expression machines. Nature 416:499–506
Martin C, Chen S, Maya-Mendoza A et al (2009) Lamin B1 maintains the functional plasticity of nucleoli. J Cell Sci 122:1551–1562
Matsuo T, Yamaguchi S, Mitsui S et al (2003) Control mechanism of the circadian clock for timing of cell division in vivo. Science 302:255–259
Misteli T (2007) Beyond the sequence: cellular organization of genome function. Cell 128:787–800
Nelson DE, Ihekwaba AE, Elliott M et al (2004) Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 306:704–708
Noordermeer D, de Laat W (2008) Joining the loops: beta-globin gene regulation. IUBMB Life 60:824–833
Osborne CS, Chakalova L, Brown KE et al (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36:1065–1071
Osborne CS, Chakalova L, Mitchell JA et al (2007) Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 8:e192
Papantonis A, Wada Y, Ohta Y et al. (2010) Changing contacts between TNFα-responsive genes point to immobilization of active RNA polymerases (Submitted)
Paschos GK, Baggs JE, Hogenesch JB et al (2010) The role of clock genes in pharmacology. Annu Rev Pharmacol Toxicol 50:187–214
Patrinos GP, de Krom M, de Boer E et al (2004) Multiple interactions between regulatory regions are required to stabilize an active chromatin hub. Genes Dev 18:1495–1509
Phillips JE, Corces VG (2009) CTCF: Master weaver of the genome. Cell 137:1194–1211
Schirmer EC, Foisner R (2007) Proteins that associate with lamins: many faces, many functions. Exp Cell Res 313:2167–2179
Schoenfelder S, Sexton T, Chakalova L et al (2010) Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet 42:53–61
Shopland LS, Lynch CR, Peterson KA et al (2006) Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence. J Cell Biol 174:27–38
Tang CW, Maya-Mendoza A, Martin C et al (2008) The integrity of a lamin B1-dependent nucleoskeleton is a fundamental determinant of RNA synthesis in human cells. J Cell Sci 121:1014–1024
Volpi EV, Chevret E, Jones T et al (2000) Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J Cell Sci 113:1565–1576
Wada Y, Ohta Y, Xu M et al (2009) A wave of nascent transcription on activated human genes. Proc Natl Acad Sci U S A 106:18357–18361
West AG, Fraser P (2005) Remote control of gene transcription. Hum Mol Genet 14:R101–R111
Wood PA, Yang X, Hrushesky WJ (2009) Clock genes and cancer. Integr Cancer Ther 8:303–308
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Netherlands
About this chapter
Cite this chapter
Jackson, D.A. (2011). Thinking Holistically About Gene Transcription. In: Adams, N., Freemont, P. (eds) Advances in Nuclear Architecture. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9899-3_7
Download citation
DOI: https://doi.org/10.1007/978-90-481-9899-3_7
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-9898-6
Online ISBN: 978-90-481-9899-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)