Gene regulation and large-scale chromatin organization in the nucleus

Regulation of gene expression involves a number of different levels of organization in the cell nucleus. The main agents of transcriptional control are the cis-acting sequences in the immediate vicinity of a gene, which combine to form the functional unit or domain. Contacts between these sequences through the formation of chromatin loops forms the most basic level of organization. The activity of functional domains is also influenced by higher order chromatin structures that impede or permit access of factors to the genes. Epigenetic modifications can maintain and propagate these active or repressive chromatin structures across large genomic regions or even entire chromosomes. There is also evidence that transcription is organized into structures called ‘factories’ and that this can lead to inter-chromosomal contacts between genes that have the potential to influence their regulation.

[1]  E. Manders,et al.  Spatial Relationship between Transcription Sites and Chromosome Territories , 1999, The Journal of cell biology.

[2]  L. Tora,et al.  Formation of an Active Tissue-Specific Chromatin Domain Initiated by Epigenetic Marking at the Embryonic Stem Cell Stage , 2005, Molecular and Cellular Biology.

[3]  Helena Fidlerová,et al.  The nucleolus and transcription of ribosomal genes , 2004, Biology of the cell.

[4]  V. Corces,et al.  Setting the Boundaries of Chromatin Domains and Nuclear Organization , 2002, Cell.

[5]  T. Richmond,et al.  Nucleosome Arrays Reveal the Two-Start Organization of the Chromatin Fiber , 2004, Science.

[6]  Hiroshi Kimura,et al.  The transcription cycle of RNA polymerase II in living cells , 2002, The Journal of cell biology.

[7]  Cameron S. Osborne,et al.  Long-range chromatin regulatory interactions in vivo , 2002, Nature Genetics.

[8]  D. Kioussis,et al.  Human CD2 3′-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice , 1989, Cell.

[9]  N. Dillon,et al.  Mapping and functional analysis of regulatory sequences in the mouse λ5-VpreB1 domain , 2005 .

[10]  Erik Splinter,et al.  Looping and interaction between hypersensitive sites in the active beta-globin locus. , 2002, Molecular cell.

[11]  I. Grummt Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. , 2003, Genes & development.

[12]  Anne E Carpenter,et al.  Large-scale chromatin structure and function. , 1999, Current opinion in cell biology.

[13]  T. Richmond,et al.  X-ray structure of a tetranucleosome and its implications for the chromatin fibre , 2005, Nature.

[14]  F. Grosveld,et al.  The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the beta globin locus control region. , 1993, The EMBO journal.

[15]  S. Elgin,et al.  Heterochromatin and gene regulation in Drosophila. , 1996, Current opinion in genetics & development.

[16]  M. Hetzer,et al.  Pushing the envelope: structure, function, and dynamics of the nuclear periphery. , 2005, Annual review of cell and developmental biology.

[17]  G. Felsenfeld,et al.  Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci , 2001, The EMBO journal.

[18]  N. Dillon Gene autonomy: Positions, please... , 2003, Nature.

[19]  Michael Litt,et al.  The insulation of genes from external enhancers and silencing chromatin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  G. Felsenfeld,et al.  Tissue‐specific factors additively increase the probability of the all‐or‐none formation of a hypersensitive site. , 1996, The EMBO journal.

[21]  F. Baas,et al.  The Human Transcriptome Map: Clustering of Highly Expressed Genes in Chromosomal Domains , 2001, Science.

[22]  B M Turner,et al.  Identification of a conserved erythroid specific domain of histone acetylation across the α-globin gene cluster , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Webb Miller,et al.  Evolution and functional classification of vertebrate gene deserts. , 2005, Genome research.

[24]  S. Dimitrov,et al.  Higher-order structure of chromatin and chromosomes. , 2001, Current opinion in genetics & development.

[25]  D. Schübeler,et al.  Methylation of histones: playing memory with DNA. , 2005, Current opinion in cell biology.

[26]  Xiang-Jiao Yang,et al.  Lysine acetylation and the bromodomain: a new partnership for signaling , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[27]  A. Pombo,et al.  Transcription factories: quantitative studies of nanostructures in the mammalian nucleus , 2004, Chromosome Research.

[28]  Eric Gilson,et al.  Insulator dynamics and the setting of chromatin domains , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  J. McNally,et al.  The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. , 2000, Science.

[30]  N. Brockdorff,et al.  Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. , 2003, Developmental cell.

[31]  Edith Heard,et al.  Recent advances in X-chromosome inactivation. , 2004, Current opinion in cell biology.

[32]  P. Becker,et al.  Reconstitution of hyperacetylated, DNase I-sensitive chromatin characterized by high conformational flexibility of nucleosomal DNA. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Groudine,et al.  The beta-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse beta-globin locus. , 1998, Molecular cell.

[34]  S. Liebhaber,et al.  Bystander gene activation by a locus control region , 2004, The EMBO journal.

[35]  J. Strouboulis,et al.  Heterochromatin Effects on the Frequency and Duration of LCR-Mediated Gene Transcription , 1996, Cell.

[36]  N. Dillon,et al.  Functional gene expression domains: defining the functional unit of eukaryotic gene regulation. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[37]  R. Flavell,et al.  Interchromosomal associations between alternatively expressed loci , 2005, Nature.

[38]  M. Hindley Pushing the envelope , 1997 .

[39]  N. Dillon,et al.  Analysis of Mice with Single and Multiple Copies of Transgenes Reveals a Novel Arrangement for the λ5-VpreB1 Locus Control Region , 1999, Molecular and Cellular Biology.

[40]  D. Kioussis,et al.  Locus Control Region Function and Heterochromatin-Induced Position Effect Variegation , 1996, Science.

[41]  G. Kollias,et al.  Position-independent, high-level expression of the human β-globin gene in transgenic mice , 1987, Cell.

[42]  D. Kioussis,et al.  Modulation of Heterochromatin Protein 1 Dynamics in Primary Mammalian Cells , 2003, Science.

[43]  S. Grewal,et al.  Regulation of heterochromatin by histone methylation and small RNAs. , 2004, Current opinion in cell biology.

[44]  Cameron S. Osborne,et al.  Active genes dynamically colocalize to shared sites of ongoing transcription , 2004, Nature Genetics.

[45]  W. Bickmore,et al.  Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. , 2004, Genes & development.

[46]  A. Spradling Transposable elements and the evolution of heterochromatin. , 1994, Society of General Physiologists series.

[47]  M. Groudine,et al.  The β-Globin LCR Is Not Necessary for an Open Chromatin Structure or Developmentally Regulated Transcription of the Native Mouse β-Globin Locus , 1998 .

[48]  Barbara L. Billington,et al.  Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription , 1990, Cell.

[49]  A. Murray,et al.  Interphase chromosomes undergo constrained diffusional motion in living cells , 1997, Current Biology.

[50]  J. Martens,et al.  Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. , 2003, Molecular cell.

[51]  N. Dillon,et al.  Transcription Factor Dosage Affects Changes in Higher Order Chromatin Structure Associated with Activation of a Heterochromatic Gene , 2000, Cell.

[52]  K. H. Wolfe,et al.  Clusters of co-expressed genes in mammalian genomes are conserved by natural selection. , 2005, Molecular biology and evolution.

[53]  Pamela A. Silver,et al.  Genome-Wide Localization of the Nuclear Transport Machinery Couples Transcriptional Status and Nuclear Organization , 2004, Cell.

[54]  I. Grummt,et al.  Cellular Stress and Nucleolar Function , 2005, Cell cycle.

[55]  S. Gasser,et al.  From snapshots to moving pictures: new perspectives on nuclear organization. , 2001, Trends in cell biology.

[56]  B. Wakimoto,et al.  Heterochromatin and gene expression in Drosophila. , 1995, Annual review of genetics.

[57]  M. Groudine,et al.  Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Jan H. Vogel,et al.  Chromosomal clustering of a human transcriptome reveals regulatory background , 2005, BMC Bioinformatics.

[59]  S. Elgin,et al.  Analyzing heterochromatin formation using chromosome 4 of Drosophila melanogaster. , 2004, Cold Spring Harbor symposia on quantitative biology.

[60]  R. Kelley Path to equality strewn with roX. , 2004, Developmental biology.

[61]  J. Strouboulis,et al.  The effect of distance on long-range chromatin interactions. , 1997, Molecular cell.

[62]  A. Riggs,et al.  The chicken lysozyme chromatin domain contains a second, widely expressed gene. , 2002, Nucleic acids research.

[63]  J. B. Rattner,et al.  The higher-order structure of chromatin: evidence for a helical ribbon arrangement , 1984, The Journal of cell biology.

[64]  Wendy A. Bickmore,et al.  Spatial organization of active and inactive genes and noncoding DNA within chromosome territories , 2002, The Journal of cell biology.

[65]  N. Shinkura,et al.  Pushing the envelope: chromatin boundaries at the nuclear pore. , 2002, Molecular cell.

[66]  R. Sternglanz,et al.  Perinuclear localization of chromatin facilitates transcriptional silencing , 1998, Nature.

[67]  Ruth R. E. Williams Transcription and the territory: the ins and outs of gene positioning. , 2003, Trends in genetics : TIG.

[68]  Anne E Carpenter,et al.  Common Effects of Acidic Activators on Large-Scale Chromatin Structure and Transcription , 2005, Molecular and Cellular Biology.

[69]  Patrick Heun,et al.  Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[70]  L. Tora,et al.  The role of enhancers as centres for general transcription factor recruitment. , 2005, Trends in biochemical sciences.

[71]  Tom Misteli,et al.  Maintenance of Stable Heterochromatin Domains by Dynamic HP1 Binding , 2003, Science.

[72]  Gerald M Rubin,et al.  Evidence for large domains of similarly expressed genes in the Drosophila genome , 2002, Journal of biology.

[73]  S. Elgin,et al.  Position effect variegation in Drosophila is associated with an altered chromatin structure. , 1995, Genes & development.

[74]  M. Groudine,et al.  Conservation of sequence and structure flanking the mouse and human β-globin loci: The β-globin genes are embedded within an array of odorant receptor genes , 1999 .

[75]  Spradling Ac Transposable elements and the evolution of heterochromatin. , 1994 .