Chromatin loops in gene regulation.

The control of gene expression involves regulatory elements that can be very far from the genes they control. Several recent technological advances have allowed the direct detection of chromatin loops that juxtapose distant genomic sites in the nucleus. Here we review recent studies from various model organisms that have provided new insights into the functions of chromatin loops and the mechanisms that form them. We discuss the widespread impact of chromatin loops on gene activation, repression, genomic imprinting and the function of enhancers and insulators.

[1]  C. Nusbaum,et al.  Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. , 2006, Genome research.

[2]  Pierre Chartrand,et al.  Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology , 2006, Chromosome Research.

[3]  M. Groudine,et al.  Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. , 2005, Molecular cell.

[4]  M. Gabut,et al.  Inheritance of Polycomb-dependent chromosomal interactions in Drosophila. , 2003, Genes & development.

[5]  M. Levine,et al.  Visualization of trans-homolog enhancer-promoter interactions at the Abd-B Hox locus in the Drosophila embryo. , 2004, Developmental cell.

[6]  M. Kladde,et al.  Interaction between transcription regulatory regions of prolactin chromatin. , 1993, Science.

[7]  Wolf Reik,et al.  Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops , 2004, Nature Genetics.

[8]  Jennifer A. Mitchell,et al.  Transcription factories are nuclear subcompartments that remain in the absence of transcription. , 2008, Genes & development.

[9]  J. D. Engel,et al.  Looping, Linking, and Chromatin Activity New Insights into β-globin Locus Regulation , 2000, Cell.

[10]  F. Winston,et al.  Analysis of Transcriptional Activation at a Distance in Saccharomyces cerevisiae , 2007, Molecular and Cellular Biology.

[11]  Davide Marenduzzo,et al.  What are the molecular ties that maintain genomic loops? , 2007, Trends in genetics : TIG.

[12]  Hui Ling Chen,et al.  CTCF Mediates Interchromosomal Colocalization Between Igf2/H19 and Wsb1/Nf1 , 2006, Science.

[13]  Rolf Ohlsson,et al.  CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Job Dekker,et al.  The three 'C' s of chromosome conformation capture: controls, controls, controls , 2005, Nature Methods.

[15]  Wouter de Laat,et al.  CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. , 2006, Genes & development.

[16]  Jan-Fang Cheng,et al.  Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome , 2005, Nature Genetics.

[17]  U. K. Laemmli,et al.  Metaphase chromosome structure: Evidence for a radial loop model , 1979, Cell.

[18]  Giacomo Cavalli,et al.  RNAi Components Are Required for Nuclear Clustering of Polycomb Group Response Elements , 2006, Cell.

[19]  A. Dejean,et al.  Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus , 2007, Nature Cell Biology.

[20]  R. Maeda,et al.  Probing long-distance regulatory interactions in the Drosophila melanogaster bithorax complex using Dam identification , 2006, Nature Genetics.

[21]  A. Martelli,et al.  The controversial nuclear matrix: a balanced point of view. , 2002, Histology and histopathology.

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

[23]  P. Fraser.  Transcriptional control thrown for a loop. , 2006, Current opinion in genetics & development.

[24]  N. Negre,et al.  PRE-mediated bypass of two Su(Hw) insulators targets PcG proteins to a downstream promoter. , 2006, Developmental cell.

[25]  I. Talianidis,et al.  Dynamics of enhancer-promoter communication during differentiation-induced gene activation. , 2002, Molecular cell.

[26]  J. Chung,et al.  Analysis of the H19ICR Insulator , 2007, Molecular and Cellular Biology.

[27]  G. Felsenfeld,et al.  CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. , 2004, Molecular cell.

[28]  F. Grosveld,et al.  β-Globin Active Chromatin Hub Formation in Differentiating Erythroid Cells and in p45 NF-E2 Knock-out Mice* , 2007, Journal of Biological Chemistry.

[29]  M. Groudine,et al.  Looping versus linking: toward a model for long-distance gene activation. , 1999, Genes & development.

[30]  Job Dekker,et al.  Gene Regulation in the Third Dimension , 2008, Science.

[31]  W. de Laat,et al.  Maintenance of Long-Range DNA Interactions after Inhibition of Ongoing RNA Polymerase II Transcription , 2008, PloS one.

[32]  M. Hampsey,et al.  A transcription-independent role for TFIIB in gene looping. , 2007, Molecular cell.

[33]  M. Groudine,et al.  A Complex Chromatin Landscape Revealed by Patterns of Nuclease Sensitivity and Histone Modification within the Mouse β-Globin Locus , 2003, Molecular and Cellular Biology.

[34]  C. Glass,et al.  RETRACTED: Nuclear Receptor-Enhanced Transcription Requires Motor- and LSD1-Dependent Gene Networking in Interchromatin Granules , 2008, Cell.

[35]  V. Corces,et al.  The role of insulator elements in large-scale chromatin structure in interphase. , 2007, Seminars in cell & developmental biology.

[36]  S. Orkin,et al.  Distinct Domains of the GATA-1 Cofactor FOG-1 Differentially Influence Erythroid versus Megakaryocytic Maturation , 2002, Molecular and Cellular Biology.

[37]  U. K. Laemmli,et al.  Chromatin Boundaries in Budding Yeast The Nuclear Pore Connection , 2002, Cell.

[38]  J. Griffith,et al.  Termination Factor-Mediated DNA Loop between Termination and Initiation Sites Drives Mitochondrial rRNA Synthesis , 2005, Cell.

[39]  Wouter de Laat,et al.  The β-globin nuclear compartment in development and erythroid differentiation , 2003, Nature Genetics.

[40]  J. T. Kadonaga,et al.  Going the distance: a current view of enhancer action. , 1998, Science.

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

[42]  V. Corces,et al.  Visualization of chromatin domains created by the gypsy insulator of Drosophila , 2003, The Journal of cell biology.

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

[44]  A. Dean,et al.  An insulator blocks spreading of histone acetylation and interferes with RNA polymerase II transfer between an enhancer and gene. , 2004, Nucleic acids research.

[45]  Chiara Lanzuolo,et al.  Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex , 2007, Nature Cell Biology.

[46]  Roy Riblet,et al.  Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. , 2005, Genes & development.

[47]  J. Dekker,et al.  Capturing Chromosome Conformation , 2002, Science.

[48]  Wendy A Bickmore,et al.  Does looping and clustering in the nucleus regulate gene expression? , 2004, Current opinion in cell biology.

[49]  Mark Groudine,et al.  Form follows function: The genomic organization of cellular differentiation. , 2004, Genes & development.

[50]  B. Steensel,et al.  Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C) , 2006, Nature Genetics.

[51]  J. French,et al.  Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene , 2008, Proceedings of the National Academy of Sciences.

[52]  M. Kagey,et al.  The Polycomb Protein Pc2 Is a SUMO E3 , 2003, Cell.

[53]  Michael Hampsey,et al.  A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping. , 2005, Genes & development.

[54]  P. Schedl,et al.  Protein:protein interactions and the pairing of boundary elements in vivo. , 2003, Genes & development.

[55]  J. D. Engel,et al.  The beta-globin stage selector element factor is erythroid-specific promoter/enhancer binding protein NF-E4. , 1989, Genes & Development.

[56]  S. Grewal,et al.  A Role for TFIIIC Transcription Factor Complex in Genome Organization , 2006, Cell.

[57]  M. Groudine,et al.  Regulation of β-globin gene expression: straightening out the locus , 1996 .

[58]  E. Bresnick,et al.  Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[59]  F. Grosveld,et al.  The active spatial organization of the beta-globin locus requires the transcription factor EKLF. , 2004, Genes & development.

[60]  V. Corces,et al.  The ubiquitin ligase dTopors directs the nuclear organization of a chromatin insulator. , 2005, Molecular cell.

[61]  D. Higgs,et al.  Long‐range chromosomal interactions regulate the timing of the transition between poised and active gene expression , 2007 .

[62]  T. Aune,et al.  Dynamic alterations in the conformation of the Ifng gene region during T helper cell differentiation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[63]  W. Reik,et al.  Deletion of a silencer element in Igf2 results in loss of imprinting independent of H19 , 2000, Nature Genetics.

[64]  V. Corces,et al.  RNA interference machinery influences the nuclear organization of a chromatin insulator , 2006, Nature Genetics.

[65]  M. Bartolomei,et al.  Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. , 1998, Genes & development.

[66]  K. Sandhu,et al.  Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions , 2006, Nature Genetics.

[67]  M. Giacca,et al.  Transcription-Dependent Gene Looping of the HIV-1 Provirus Is Dictated by Recognition of Pre-mRNA Processing Signals , 2008, Molecular cell.

[68]  Thomas Cremer,et al.  Chromosome territories--a functional nuclear landscape. , 2006, Current opinion in cell biology.

[69]  S. Henikoff,et al.  Identification of in vivo DNA targets of chromatin proteins using tethered Dam methyltransferase , 2000, Nature Biotechnology.

[70]  S. Orkin,et al.  Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains , 1995, Molecular and cellular biology.

[71]  Xiangdong Fang,et al.  Locus control regions. , 2002, Blood.

[72]  Richard Axel,et al.  Interchromosomal Interactions and Olfactory Receptor Choice , 2006, Cell.

[73]  P. Georgiev,et al.  ‘Insulator bodies’ are aggregates of proteins but not of insulators , 2008, EMBO reports.

[74]  G. Fourel,et al.  A Methyltransferase Targeting Assay Reveals Silencer-Telomere Interactions in Budding Yeast , 2003, Molecular and Cellular Biology.

[75]  G. Morgan.  Lampbrush chromosomes and associated bodies: new insights into principles of nuclear structure and function , 2004, Chromosome Research.

[76]  R. Flavell,et al.  Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions , 2005, Nature Immunology.

[77]  H. Strutt,et al.  The Distribution of Polycomb-Group Proteins During Cell Division and Development in Drosophila Embryos: Impact on Models for Silencing , 1998, The Journal of cell biology.

[78]  G. Felsenfeld,et al.  Insulators: exploiting transcriptional and epigenetic mechanisms , 2006, Nature Reviews Genetics.

[79]  Antonin Morillon,et al.  Gene loops juxtapose promoters and terminators in yeast , 2004, Nature Genetics.

[80]  A. Dean.  On a chromosome far, far away: LCRs and gene expression. , 2006, Trends in genetics : TIG.

[81]  T. Kohwi-Shigematsu,et al.  SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes , 2006, Nature Genetics.

[82]  V. Corces,et al.  A chromatin insulator determines the nuclear localization of DNA. , 2000, Molecular cell.

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

[84]  T. Mahmoudi,et al.  GAGA can mediate enhancer function in trans by linking two separate DNA molecules , 2002, The EMBO journal.

[85]  Chunhui Hou,et al.  A positive role for NLI/Ldb1 in long-range beta-globin locus control region function. , 2007, Molecular cell.

[86]  G. Blobel,et al.  Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus. , 2008, Molecular cell.

[87]  W. Garrard,et al.  Long-Range Interactions between Three Transcriptional Enhancers, Active Vκ Gene Promoters, and a 3′ Boundary Sequence Spanning 46 Kilobases , 2005, Molecular and Cellular Biology.

[88]  Victor G Corces,et al.  The centrosomal protein CP190 is a component of the gypsy chromatin insulator. , 2004, Molecular cell.

[89]  G. Felsenfeld,et al.  We gather together: insulators and genome organization. , 2007, Current opinion in genetics & development.

[90]  Myles A Brown,et al.  Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. , 2005, Molecular cell.

[91]  Vip Viprakasit,et al.  A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter , 2006, Science.

[92]  Stefan L Ameres,et al.  Inducible DNA‐loop formation blocks transcriptional activation by an SV40 enhancer , 2005, The EMBO journal.

[93]  H. Heng,et al.  Re-defining the chromatin loop domain , 2001, Cytogenetic and Genome Research.

[94]  M. Hampsey,et al.  Synthetic enhancement of a TFIIB defect by a mutation in SSU72, an essential yeast gene encoding a novel protein that affects transcription start site selection in vivo , 1996, Molecular and cellular biology.

[95]  J. Strouboulis,et al.  Multiple interactions between regulatory regions are required to stabilize an active chromatin hub. , 2004, Genes & development.

[96]  Richard A Flavell,et al.  Long-range intrachromosomal interactions in the T helper type 2 cytokine locus , 2004, Nature Immunology.

[97]  T. Mahmoudi,et al.  DNA looping induced by a transcriptional enhancer in vivo , 2005, Nucleic acids research.