Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma

In mantle cell lymphoma (MCL) and some cases of multiple myeloma (MM), cyclin D1 expression is deregulated by chromosome translocations involving the immunoglobulin heavy chain (IgH) locus. To evaluate the mechanisms responsible, gene targeting was used to study long-distance gene regulation. Remarkably, these targeted cell lines lost the translocated chromosome (t(11;14)). In these MCL and MM cells, the nonrearranged cyclin D1 (CCND1) locus reverts from CpG hypomethylated to hypermethylated. Reintroduction of the translocated chromosome induced a loss of methylation at the unrearranged CCND1 locus, providing evidence of a transallelic regulatory effect. In these cell lines and primary MCL patient samples, the CCND1 loci are packaged in chromatin-containing CCCTC binding factor (CTCF) and nucleophosmin (NPM) at the nucleolus. We show that CTCF and NPM are bound at the IgH 3′ regulatory elements only in the t(11;14) MCL cell lines. Furthermore, NPM short hairpin RNA produces a specific growth arrest in these cells. Our data demonstrate transvection in human cancer and suggest a functional role for CTCF and NPM.

[1]  Jeannie T. Lee,et al.  Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein , 2007, Nature Genetics.

[2]  Jeannie T. Lee,et al.  Perinucleolar Targeting of the Inactive X during S Phase: Evidence for a Role in the Maintenance of Silencing , 2007, Cell.

[3]  V. Chandler.  Paramutation: From Maize to Mice , 2007, Cell.

[4]  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.

[5]  P. Gounon,et al.  RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse , 2006, Nature.

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

[7]  Chia-Lun Tsai,et al.  Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation , 2006, Science.

[8]  L. Staudt,et al.  Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. , 2005, Blood.

[9]  G. Guerrero,et al.  YY1 and GATA-1 Interaction Modulate the Chicken 3′-Side α-Globin Enhancer Activity , 2005 .

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

[11]  D. Engelke,et al.  Silencing Near tRNA Genes Requires Nucleolar Localization* , 2005, Journal of Biological Chemistry.

[12]  Victor V Lobanenkov,et al.  Chromatin Architecture near a Potential 3′ End of the Igh Locus Involves Modular Regulation of Histone Modifications during B-Cell Development and In Vivo Occupancy at CTCF Sites , 2005, Molecular and Cellular Biology.

[13]  G. Guerrero,et al.  YY1 and GATA-1 interaction modulate the chicken 3'-side alpha-globin enhancer activity. , 2005, Journal of molecular biology.

[14]  L. Staudt,et al.  Cyclin D 1 – negative mantle cell lymphoma : a clinicopathologic study based on gene expression profiling , 2005 .

[15]  C. Corless,et al.  Transplanted human bone marrow contributes to vascular endothelium. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  E. Epner,et al.  Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences. , 2004, Blood.

[17]  V. Chandler,et al.  Chromatin conversations: mechanisms and implications of paramutation , 2004, Nature Reviews Genetics.

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

[19]  R. Martienssen,et al.  Maintenance of heterochromatin by RNA interference of tandem repeats , 2003, Nature Genetics.

[20]  James M. Roberts,et al.  Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. , 2003, Molecular cell.

[21]  Michael Lu,et al.  Trans allele methylation and paramutation-like effects in mice , 2003, Nature Genetics.

[22]  R. Jaenisch,et al.  Chromosomal Instability and Tumors Promoted by DNA Hypomethylation , 2003, Science.

[23]  Xiaofeng Cao,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003, Science.

[24]  J. Kelly,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003 .

[25]  D. Rowitch,et al.  Development of mice expressing a single D-type cyclin. , 2002, Genes & development.

[26]  R. Hipskind,et al.  Oct-1 Potentiates CREB-Driven Cyclin D1 Promoter Activation via a Phospho-CREB- and CREB Binding Protein-Independent Mechanism , 2002, Molecular and Cellular Biology.

[27]  J. Kennison,et al.  Transvection and silencing of the Scr homeotic gene of Drosophila melanogaster. , 2002, Genetics.

[28]  S. Schwartz,et al.  Chromosomal autonomy of hMLH1 methylation in colon cancer. , 2002 .

[29]  F. Cuzin,et al.  Transvection effects involving DNA methylation during meiosis in the mouse , 2002, The EMBO journal.

[30]  J. Birchler,et al.  RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. , 2002, Molecular cell.

[31]  Ian W Duncan,et al.  Transvection effects in Drosophila. , 2002, Annual review of genetics.

[32]  Chris Albanese,et al.  NF-κB and cell-cycle regulation: the cyclin connection , 2001 .

[33]  A. West,et al.  Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. , 2001, Science.

[34]  H. Nishimatsu,et al.  Transcriptional Activation of the cyclin D1 Gene Is Mediated by Multiple Cis-Elements, Including SP1 Sites and a cAMP-responsive Element in Vascular Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[35]  C. Albanese,et al.  NF-kappaB and cell-cycle regulation: the cyclin connection. , 2001, Cytokine & growth factor reviews.

[36]  M. Dyer,et al.  The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies. , 2000, Blood.

[37]  G. Felsenfeld,et al.  Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene , 2000, Nature.

[38]  A. Jauch,et al.  Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32). , 2000, Blood.

[39]  E. Lam,et al.  Cyclin D3 Compensates for Loss of Cyclin D2 in Mouse B-lymphocytes Activated via the Antigen Receptor and CD40* , 2000, The Journal of Biological Chemistry.

[40]  E. Lam,et al.  Cyclin D 3 Compensates for Loss of Cyclin D 2 in Mouse B-lymphocytes Activated via the Antigen Receptor and CD 40 * , 2000 .

[41]  F. Duh,et al.  Analysis of aberrant methylation of the VHL gene by transgenes, monochromosome transfer, and cell fusion , 1999, Oncogene.

[42]  R. Kitazawa,et al.  Transcriptional Regulation of Rat Cyclin D1 Gene by CpG Methylation Status in Promoter Region* , 1999, The Journal of Biological Chemistry.

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

[44]  A. Bird,et al.  DNA methylation and chromatin modification. , 1999, Current opinion in genetics & development.

[45]  P. L. Bergsagel,et al.  Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell. , 1999, Molecular cell.

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

[47]  A. Viterbo,et al.  Position-Dependent Methylation and Transcriptional Silencing of Transgenes in Inverted T-DNA Repeats: Implications for Posttranscriptional Silencing of Homologous Host Genes in Plants , 1998, Molecular and Cellular Biology.

[48]  Y. Hosokawa,et al.  Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: Analysis of allele‐specific expression , 1998, Genes, chromosomes & cancer.

[49]  S. Henikoff,et al.  Trans-Sensing Effects: The Ups and Downs of Being Together , 1998, Cell.

[50]  E. Walker,et al.  Paramutation of the r1 locus of maize is associated with increased cytosine methylation. , 1998, Genetics.

[51]  Amanda J. Wilson,et al.  Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele , 1997, Nature Genetics.

[52]  S. Clark,et al.  Detection and measurement of PCR bias in quantitative methylation analysis of bisulphite-treated DNA. , 1997, Nucleic acids research.

[53]  W. Reik,et al.  Transactivation of Igf2 in a mouse model of Beckwith–Wiedemann syndrome , 1997, Nature.

[54]  W. Reik,et al.  Loss of the maternal H19 gene induces changes in Igf2 methylation in both cis and trans. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

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

[56]  T. Mukai,et al.  Aberrant Methylation of an Imprinted Gene U2af1-rs1(SP2) Caused by Its Own Transgene* , 1997, The Journal of Biological Chemistry.

[57]  K. Kinzler,et al.  DNA methylation and genetic instability in colorectal cancer cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[58]  E. Schuuring,et al.  The t(11;14) (q13;q32) in multiple myeloma cell line KMS12 has its 11q13 breakpoint 330 kb centromeric from the cyclin D1 gene. , 1997, Blood.

[59]  V. Colot,et al.  Interchromosomal Transfer of Epigenetic States in Ascobolus: Transfer of DNA Methylation Is Mechanistically Related to Homologous Recombination , 1996, Cell.

[60]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[61]  J. LaSalle,et al.  Homologous Association of Oppositely Imprinted Chromosomal Domains , 1996, Science.

[62]  G. Wahl,et al.  Participation of the Human β-Globin Locus Control Region in Initiation of DNA Replication , 1995, Science.

[63]  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.

[64]  F. Berger,et al.  Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas. , 1994, Blood.

[65]  H. Cedar,et al.  B cell-specific demethylation: A novel role for the intronic κ chain enhancer sequence , 1994, Cell.

[66]  H. Cedar,et al.  B cell-specific demethylation: a novel role for the intronic kappa chain enhancer sequence. , 1994, Cell.

[67]  J. Decaprio,et al.  Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes. , 1993, The Journal of biological chemistry.

[68]  W. C. Forrester,et al.  Inactivation of the human beta-globin gene by targeted insertion into the beta-globin locus control region. , 1992, Genes & development.

[69]  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.

[70]  C. Lehner,et al.  Major nucleolar proteins shuttle between nucleus and cytoplasm , 1989, Cell.

[71]  M. Abe,et al.  Characterization and comparison of two newly established epstein‐barr virus‐negative lymphoma B‐cell lines: Surface markers, growth characteristics, cytogenetics, and transplantability , 1988, Cancer.