Locus control regions.

Locus control regions (LCRs) are operationally defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number-dependent manner at ectopic chromatin sites. Although their composition and locations relative to their cognate genes are different, LCRs have been described in a broad spectrum of mammalian gene systems, suggesting that they play an important role in the control of eukaryotic gene expression. The discovery of the LCR in the beta-globin locus and the characterization of LCRs in other loci reinforces the concept that developmental and cell lineage-specific regulation of gene expression relies not on gene-proximal elements such as promoters, enhancers, and silencers exclusively, but also on long-range interactions of various cis regulatory elements and dynamic chromatin alterations.

[1]  E. Rothenberg,et al.  A New Regulatory Region of the IL-2 Locus That Confers Position-Independent Transgene Expression1 , 2001, The Journal of Immunology.

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

[3]  M. Groudine,et al.  Asynchronous DNA replication within the human beta-globin gene locus. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Kirby D. Johnson,et al.  Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter. , 2001, Molecular cell.

[5]  A. Nienhuis,et al.  Mechanism of DNase I hypersensitive site formation within the human globin locus control region. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  W. Bickmore,et al.  Pausing for Thought on the Boundaries of Imprinting , 2000, Cell.

[7]  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 .

[8]  C. Lowrey,et al.  Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region. , 1998, Nucleic acids research.

[9]  B. Emerson,et al.  A SWI/SNF–Related Chromatin Remodeling Complex, E-RC1, Is Required for Tissue-Specific Transcriptional Regulation by EKLF In Vitro , 1998, Cell.

[10]  P. Navas,et al.  Developmental Specificity of the Interaction between the Locus Control Region and Embryonic or Fetal Globin Genes in Transgenic Mice with an HS3 Core Deletion , 1998, Molecular and Cellular Biology.

[11]  E. Bresnick,et al.  Synergism between hypersensitive sites confers long-range gene activation by the beta-globin locus control region. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C. Allis,et al.  Correlation Between Histone Lysine Methylation and Developmental Changes at the Chicken β-Globin Locus , 2001, Science.

[13]  I. Thorey,et al.  Transcriptional insulation of the human keratin 18 gene in transgenic mice , 1993, Molecular and cellular biology.

[14]  T. Enver,et al.  Targeting gene expression to haemopoietic stem cells: a chromatin‐dependent upstream element mediates cell type‐specific expression of the stem cell antigen CD34. , 1995, The EMBO journal.

[15]  M. Groudine,et al.  β-globin Gene Switching and DNase I Sensitivity of the Endogenous β-globin Locus in Mice Do Not Require the Locus Control Region , 2000 .

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

[17]  J. Widom,et al.  Effects of core histone tail domains on the equilibrium constants for dynamic DNA site accessibility in nucleosomes. , 2000, Journal of molecular biology.

[18]  G. Stamatoyannopoulos,et al.  Evidence that DNase I hypersensitive site 5 of the human beta-globin locus control region functions as a chromosomal insulator in transgenic mice. , 2002, Nucleic Acids Research.

[19]  S. Warming,et al.  A minimal c-fes cassette directs myeloid-specific expression in transgenic mice. , 2000, Blood.

[20]  D. Chourrout,et al.  Stable and full rescue of the pigmentation in a medaka albino mutant by transfer of a 17 kb genomic clone containing the medaka tyrosinase gene. , 2000, Gene.

[21]  T. Ley,et al.  Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. West,et al.  Conserved CTCF Insulator Elements Flank the Mouse and Human β-Globin Loci , 2002, Molecular and Cellular Biology.

[23]  F. Grosveld,et al.  The human beta‐globin gene contains multiple regulatory regions: identification of one promoter and two downstream enhancers. , 1988, The EMBO journal.

[24]  S. Liebhaber,et al.  The human growth hormone gene is regulated by a multicomponent locus control region , 1995, Molecular and cellular biology.

[25]  S. Liebhaber,et al.  The Human Growth Hormone Gene Cluster Locus Control Region Supports Position-independent Pituitary- and Placenta-specific Expression in the Transgenic Mouse* , 2000, The Journal of Biological Chemistry.

[26]  W. C. Forrester,et al.  A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. , 1990, Genes & development.

[27]  Y. ChanJ,et al.  酵母での遺伝的選択によるNF-E2関連転写因子、Nrf1のクローニング , 1993 .

[28]  D. Tuan,et al.  Transcription of the hypersensitive site HS2 enhancer in erythroid cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[30]  J. Stamatoyannopoulos,et al.  Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element , 1994, Molecular and cellular biology.

[31]  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.

[32]  F. Grosveld,et al.  The 5′HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF‐E2 binding sites. , 1991, The EMBO journal.

[33]  D. Kioussis,et al.  Beta-globin gene inactivation by DNA translocation in gamma beta-thalassaemia. , 1983, Nature.

[34]  S. Orkin,et al.  Dependence of globin gene expression in mouse erythroleukemia cells on the NF-E2 heterodimer , 1995, Molecular and cellular biology.

[35]  M. Obinata,et al.  Inducible expression of erythroid-specific mouse glycophorin gene is regulated by proximal elements and locus control region-like sequence. , 1995, Journal of biochemistry.

[36]  M. Groudine,et al.  Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region. , 2000, Molecular cell.

[37]  D. Tuan,et al.  The "beta-like-globin" gene domain in human erythroid cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[38]  C. Lowrey,et al.  In Vivo Formation of a Human β-Globin Locus Control Region Core Element Requires Binding Sites for Multiple Factors Including GATA-1, NF-E2, Erythroid Kruppel-like Factor, and Sp1* , 2001, The Journal of Biological Chemistry.

[39]  K. Ozato,et al.  A 150-base pair 5' region of the MHC class I HLA-B7 gene is sufficient to direct tissue-specific expression and locus control region activity: the alpha site determines efficient expression and in vivo occupancy at multiple cis-active sites throughout this region. , 1997, Journal of immunology.

[40]  A. Nienhuis,et al.  Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells. , 1990, Genes & development.

[41]  Rajesh Bagga,et al.  HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology , 2000, Nucleic Acids Res..

[42]  G. Jiménez,et al.  The mouse β-globin locus control region: hypersensitive sites 3 and 4 , 1992 .

[43]  I. Simon,et al.  Developmental regulation of DNA replication timing at the human β globin locus , 2001 .

[44]  T. Stocker The Seesaw Effect , 1998, Science.

[45]  I. Simon,et al.  12 Temporal Order of DNA Replication , 1996 .

[46]  S. Orkin,et al.  In vivo protein-DNA interactions at hypersensitive site 3 of the human beta-globin locus control region. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Y. Kan,et al.  Synergistic enhancement of globin gene expression by activator protein-1-like proteins. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[48]  T. Ley,et al.  Structure and function of the murine β-globin locus control region 5′ HS-3 , 1992 .

[49]  I. Simon,et al.  Developmental regulation of DNA replication timing at the human beta globin locus. , 2001, The EMBO journal.

[50]  I. Hampson,et al.  Upstream elements bestow T-cell and haemopoietic progenitor-specific activity on the granzyme B promoter. , 1999, Gene.

[51]  R. Takahashi,et al.  Position‐independent and high‐level expression of human α‐lactalbumin in the milk of transgenic rats carrying a 210‐kb YAC DNA , 1997, Molecular reproduction and development.

[52]  J. Roder,et al.  Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  Holmquist Gp Role of replication time in the control of tissue-specific gene expression. , 1987 .

[54]  G. Stamatoyannopoulos,et al.  Primary structure of the goat β-globin locus control region , 1991 .

[55]  C. Ford,et al.  The gamma 1 heavy chain gene includes all of the cis-acting elements necessary for expression of properly regulated germ-line transcripts. , 1996, Journal of immunology.

[56]  J. D. Engel,et al.  The world according to Maf. , 1997, Nucleic acids research.

[57]  J. D. Engel,et al.  Hypersensitive Site 2 Specifies a Unique Function within the Human β-Globin Locus Control Region To Stimulate Globin Gene Transcription , 1999, Molecular and Cellular Biology.

[58]  G. Stamatoyannopoulos,et al.  Role of gene order in developmental control of human gamma- and beta-globin gene expression , 1993, Molecular and cellular biology.

[59]  L. Madisen,et al.  Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells. , 1994, Genes & development.

[60]  F. Grosveld,et al.  The beta-globin dominant control region. , 1989, Progress in clinical and biological research.

[61]  S. Gitelman,et al.  A promoter within intron 35 of the human C4A gene initiates abundant adrenal-specific transcription of a 1 kb RNA: location of a cryptic CYP21 promoter element? , 1995, Human molecular genetics.

[62]  R. Hammer,et al.  Tissue-specific expression of kallikrein family transgenes in mice and rats. , 1992, DNA and cell biology.

[63]  T. Townes,et al.  Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression. , 1994, Nucleic acids research.

[64]  T. Jenuwein,et al.  The immunoglobulin mu enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation. , 1993, Genes & development.

[65]  M. Reitman,et al.  Site-independent expression of the chicken βA-globin gene in transgenic mice , 1990, Nature.

[66]  Félix Recillas-Targa,et al.  Position-effect protection and enhancer blocking by the chicken β-globin insulator are separable activities , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[67]  C. Schildkraut,et al.  Activation and repression of a beta-globin gene in cell hybrids is accompanied by a shift in its temporal replication , 1989, Molecular and cellular biology.

[68]  J. Richardson,et al.  A 500-bp region, ≈40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice , 1999 .

[69]  E. Bresnick,et al.  Direct interaction of NF-E2 with hypersensitive site 2 of the beta-globin locus control region in living cells. , 2000, Blood.

[70]  F. Grosveld Activation by locus control regions? , 1999, Current opinion in genetics & development.

[71]  James T. Elder,et al.  A developmentally stable chromatin structure in the human beta-globin gene cluster. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[72]  F. Grosveld,et al.  Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta-globin locus control region in vivo. , 1998, Genes & development.

[73]  F. Costantini,et al.  Developmental regulation of a cloned adult beta-globin gene in transgenic mice. , 1985, Nature.

[74]  M. Groudine,et al.  Long-Distance Control of Origin Choice and Replication Timing in the Human β-Globin Locus Are Independent of the Locus Control Region , 2000, Molecular and Cellular Biology.

[75]  T. Ley,et al.  Independent formation of DnaseI hypersensitive sites in the murine beta-globin locus control region. , 2000, Blood.

[76]  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.

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

[78]  F. Grosveld,et al.  Detailed analysis of the site 3 region of the human beta‐globin dominant control region. , 1990, The EMBO journal.

[79]  A. E. Sippel,et al.  Tissue specific and position independent expression of the complete gene domain for chicken lysozyme in transgenic mice. , 1990, The EMBO journal.

[80]  F. Grosveld,et al.  The beta‐globin dominant control region: hypersensitive site 2. , 1990, The EMBO journal.

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

[82]  Peter Fraser,et al.  Transcription complex stability and chromatin dynamics in vivo , 1995, Nature.

[83]  B. Alter,et al.  Gamma delta beta-thalassemia due to a de novo mutation deleting the 5' beta-globin gene activation-region hypersensitive sites. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[84]  F. Grosveld,et al.  Locus control regions, chromatin activation and transcription. , 1998, Current opinion in cell biology.

[85]  G. Stamatoyannopoulos,et al.  Hypersensitive site 5 of the human beta locus control region functions as a chromatin insulator. , 1994, Blood.

[86]  F. Grosveld,et al.  The human beta-globin locus control region confers an early embryonic erythroid-specific expression pattern to a basic promoter driving the bacterial lacZ gene. , 1996, Development.

[87]  F. Grosveld,et al.  Importance of globin gene order for correct developmental expression. , 1991, Genes & development.

[88]  A. Winoto,et al.  Adjacent DNA elements dominantly restrict the ubiquitous activity of a novel chromatin‐opening region to specific tissues , 1997, The EMBO journal.

[89]  W Miller,et al.  The complete sequences of the galago and rabbit beta-globin locus control regions: extended sequence and functional conservation outside the cores of DNase hypersensitive sites. , 1997, Genomics.

[90]  M. Athanasiou,et al.  Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice. Evidence for a positive regulatory region located 1 kilobase 5' to the start site of transcription. , 1993, Journal of immunology.

[91]  F. Grosveld,et al.  A dominant chromatin‐opening activity in 5′ hypersensitive site 3 of the human beta‐globin locus control region. , 1996, The EMBO journal.

[92]  C. Goodman,et al.  The Molecular Biology of Axon Guidance , 1996, Science.

[93]  M. Reitman,et al.  Control of globin gene transcription. , 1990, Annual review of cell biology.

[94]  M. Wiles,et al.  Far upstream regions of class II MHC Ea are necessary for position-independent, copy-dependent expression of Ea transgene. , 1993, Nucleic acids research.

[95]  B. Emerson,et al.  An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro. , 1997, Genes & development.

[96]  S. Orkin,et al.  Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[97]  B. Emerson,et al.  NF-E2 disrupts chromatin structure at human beta-globin locus control region hypersensitive site 2 in vitro , 1996, Molecular and cellular biology.

[98]  D. Dorsett,et al.  Distant liaisons: long-range enhancer-promoter interactions in Drosophila. , 1999, Current opinion in genetics & development.

[99]  A. Winoto,et al.  Function and Factor Interactions of a Locus Control Region Element in the Mouse T Cell Receptor-α/Dad1 Gene Locus1 , 2001, The Journal of Immunology.

[100]  T. Dale,et al.  High-level expression of the rat whey acidic protein gene is mediated by elements in the promoter and 3' untranslated region , 1992, Molecular and cellular biology.

[101]  U. Schibler,et al.  The 5' flanking region of the rat LAP (C/EBP beta) gene can direct high-level, position-independent, copy number-dependent expression in multiple tissues in transgenic mice. , 1994, Nucleic acids research.

[102]  F. Grosveld,et al.  Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. , 1989, Nucleic acids research.

[103]  S. Rowan,et al.  Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[104]  M. Reitman,et al.  An enhancer/locus control region is not sufficient to open chromatin , 1993, Molecular and cellular biology.

[105]  P. Reddy,et al.  Protein-DNA interactions in vivo of an erythroid-specific, human beta-globin locus enhancer. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[106]  A. Winoto,et al.  A locus control region in the T cell receptor alpha/delta locus. , 1994, Immunity.

[107]  W. C. Forrester,et al.  Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids. , 1987, Nucleic acids research.

[108]  M. Carey,et al.  The Enhanceosome and Transcriptional Synergy , 1998, Cell.

[109]  S. Liebhaber,et al.  Targeted Recruitment of Histone Acetyltransferase Activity to a Locus Control Region* , 2000, The Journal of Biological Chemistry.

[110]  D. Ward,et al.  Delineation of DNA replication time zones by fluorescence in situ hybridization. , 1992, The EMBO journal.

[111]  Y. Kan,et al.  Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[112]  F. Grosveld,et al.  The β-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner , 1989, Cell.

[113]  G. Kollias,et al.  Regulated expression of human A γ-, β-, and hybrid γβ-globin genes in transgenic mice: Manipulation of the developmental expression patterns , 1986, Cell.

[114]  J. Richardson,et al.  A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[115]  M. Groudine,et al.  Activation of β-major globin gene transcription is associated with recruitment of NF-E2 to the β-globin LCR and gene promoter , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[116]  David A. Willoughby,et al.  An Alu Element from the K18 Gene Confers Position-independent Expression in Transgenic Mice* , 2000, The Journal of Biological Chemistry.

[117]  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 .

[118]  A. Monaghan,et al.  A cell‐specific enhancer far upstream of the mouse tyrosinase gene confers high level and copy number‐related expression in transgenic mice. , 1994, The EMBO journal.

[119]  G. Stamatoyannopoulos,et al.  Structural analysis and mapping of DNase I hypersensitivity of HS5 of the beta-globin locus control region. , 1999, Genomics.

[120]  C. Whitelaw,et al.  Position-independent expression of the ovine beta-lactoglobulin gene in transgenic mice. , 1992, The Biochemical journal.

[121]  Johnm . Taylor,et al.  Structure of the Hepatic Control Region of the Human Apolipoprotein E/C-I Gene Locus (*) , 1995, The Journal of Biological Chemistry.

[122]  R. Flavell,et al.  Regulated expression of the human β-globin gene family in murine erythroleukaemia cells , 1983, Nature.

[123]  S. Spicuglia,et al.  Chromatin remodeling by the T cell receptor (TCR)-beta gene enhancer during early T cell development: Implications for the control of TCR-beta locus recombination. , 2000, The Journal of experimental medicine.

[124]  J. Locke,et al.  Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect. , 1988, Genetics.

[125]  S. Hedrick,et al.  Elf-1 binds to a critical element in a second CD4 enhancer , 1994, Molecular and cellular biology.

[126]  G. Stamatoyannopoulos,et al.  Beta-globin locus activation regions: conservation of organization, structure, and function. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[127]  R. Palmiter,et al.  Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice , 1993, Molecular and cellular biology.

[128]  H. Rindt,et al.  Position independent expression and developmental regulation is directed by the beta myosin heavy chain gene's 5' upstream region in transgenic mice. , 1995, Nucleic acids research.

[129]  J. McDowell,et al.  Essential role of NF-E2 in remodeling of chromatin structure and transcriptional activation of the epsilon-globin gene in vivo by 5' hypersensitive site 2 of the beta-globin locus control region , 1996, Molecular and cellular biology.

[130]  M. Groudine,et al.  The murine β-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[131]  T. Ikuta,et al.  In vivo protein-DNA interactions at the beta-globin gene locus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[132]  G. Felsenfeld,et al.  A 5′ element of the chicken β-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila , 1993, Cell.

[133]  B. Aronow,et al.  Functional analysis of the human adenosine deaminase gene thymic regulatory region and its ability to generate position-independent transgene expression , 1992, Molecular and cellular biology.

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

[135]  F. Grosveld,et al.  Chromatin interaction mechanism of transcriptional control in vivo , 1998, The EMBO journal.

[136]  T. Mukai,et al.  Position-independent, high-level, and correct regional expression of the rat aldolase C gene in the central nervous system of transgenic mice. , 1994, European journal of biochemistry.

[137]  Frank R. Lin,et al.  Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. , 2002, Molecular cell.

[138]  W. Dunnick,et al.  A DNase I hypersensitive site near the murine gamma1 switch region contributes to insertion site independence of transgenes and modulates the amount of transcripts induced by CD40 ligation. , 2000, International immunology.

[139]  S. Raguz,et al.  Muscle-specific locus control region activity associated with the human desmin gene. , 1998, Developmental biology.

[140]  M. Groudine,et al.  Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta-globin locus. , 2000, Genes & development.

[141]  Joonsoo Kang,et al.  A Novel Element Upstream of the Vγ2 Gene in the Murine T Cell Receptor γ Locus Cooperates with the 3′ Enhancer to Act as a Locus Control Region , 1999, The Journal of experimental medicine.

[142]  R. Gelinas,et al.  Characterization of a DNA binding activity in DNAse I hypersensitive site 4 of the human globin locus control region. , 1991, Nucleic acids research.

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

[144]  G. Felsenfeld Chromatin structure and the expression of globin-encoding genes. , 1993, Gene.

[145]  H. Ashe,et al.  Intergenic transcription and transinduction of the human beta-globin locus. , 1997, Genes & development.

[146]  Wenjun Zhang,et al.  Site-Specific Acetylation by p300 or CREB Binding Protein Regulates Erythroid Krüppel-Like Factor Transcriptional Activity via Its Interaction with the SWI-SNF Complex , 2001, Molecular and Cellular Biology.

[147]  J. Lingrel,et al.  Erythroid‐specific expression of human beta‐globin genes in transgenic mice. , 1985, The EMBO journal.

[148]  J. Widom,et al.  Sequence and position-dependence of the equilibrium accessibility of nucleosomal DNA target sites. , 2000, Journal of molecular biology.

[149]  Arthur W. Nienhuis,et al.  Hemoglobin switching , 1978, Cell.

[150]  M. Groudine,et al.  The Locus Control Region Is Necessary for Gene Expression in the Human β-Globin Locus but Not the Maintenance of an Open Chromatin Structure in Erythroid Cells , 1998, Molecular and Cellular Biology.

[151]  M. Reitman,et al.  Site-independent expression of the chicken beta A-globin gene in transgenic mice. , 1990, Nature.

[152]  K. Itoh,et al.  Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site , 1996, Molecular and cellular biology.

[153]  A. Winoto,et al.  A New Element within the T-Cell Receptor α Locus Required for Tissue-Specific Locus Control Region Activity , 1999, Molecular and Cellular Biology.

[154]  F. Mills,et al.  Enhancer Complexes Located Downstream of Both Human Immunoglobulin Cα Genes , 1997, The Journal of experimental medicine.

[155]  J. D. Engel,et al.  Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4. , 1995, Genes & development.

[156]  T. Kimbrough,et al.  Effect of deletion of 5'HS3 or 5'HS2 of the human beta-globin locus control region on the developmental regulation of globin gene expression in beta-globin locus yeast artificial chromosome transgenic mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[157]  G. Kollias,et al.  Regulated expression of human A gamma-, beta-, and hybrid gamma beta-globin genes in transgenic mice: manipulation of the developmental expression patterns. , 1986, Cell.

[158]  R. Shivdasani,et al.  Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2. , 1998, Blood.

[159]  J. Stamatoyannopoulos,et al.  NF‐E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta‐globin locus control region. , 1995, The EMBO journal.

[160]  A. Winoto,et al.  Control of Organ-specific Demethylation by an Element of the T-cell Receptor-α Locus Control Region* , 2000, The Journal of Biological Chemistry.

[161]  A. West,et al.  Conserved CTCF insulator elements flank the mouse and human beta-globin loci. , 2002, Molecular and cellular biology.

[162]  M. Kalos,et al.  Position-independent transgene expression mediated by boundary elements from the apolipoprotein B chromatin domain , 1995, Molecular and cellular biology.

[163]  F. Grosveld,et al.  Hypersensitive site 4 of the human β globin locus control region , 1991 .

[164]  Qiliang Li,et al.  Locus control regions: coming of age at a decade plus. , 1999, Trends in genetics : TIG.

[165]  R. Krumlauf,et al.  Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. , 1987, Science.

[166]  G. Stamatoyannopoulos,et al.  A chromatin insulator protects retrovirus vectors from chromosomal position effects. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[167]  R. Palmiter,et al.  Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

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

[169]  S. Agarwal,et al.  Long-range transcriptional regulation of cytokine gene expression. , 1998, Current opinion in immunology.

[170]  J. D. Engel,et al.  Effects of altered gene order or orientation of the locus control region on human β-globin gene expression in mice , 1999, Nature.

[171]  S. Liebhaber,et al.  Patterns of histone acetylation suggest dual pathways for gene activation by a bifunctional locus control region , 2000, The EMBO journal.

[172]  W Miller,et al.  Locus control regions of mammalian beta-globin gene clusters: combining phylogenetic analyses and experimental results to gain functional insights. , 1997, Gene.

[173]  F. Costantini,et al.  Developmental regulation of a cloned adult β-globin gene in transgenic mice , 1985, Nature.

[174]  Donald J. Zack,et al.  A locus control region adjacent to the human red and green visual pigment genes , 1992, Neuron.

[175]  L. Madisen,et al.  The Immunoglobulin Heavy Chain Locus Control Region Increases Histone Acetylation along Linked c-myc Genes , 1998, Molecular and Cellular Biology.

[176]  S. Baylin,et al.  DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci , 2000, Nature Genetics.

[177]  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.

[178]  Y. Kan,et al.  Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[179]  A. West,et al.  The Protein CTCF Is Required for the Enhancer Blocking Activity of Vertebrate Insulators , 1999, Cell.

[180]  Paul Tempst,et al.  Erythroid transcription factor NF-E2 is a haematopoietic-specific basic–leucine zipper protein , 1993, Nature.

[181]  S. Liebhaber,et al.  A defined locus control region determinant links chromatin domain acetylation with long-range gene activation. , 2002, Molecular cell.