Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell chronic lymphocytic leukemia.

Chromosome 13q14 deletions constitute the most common structural aberration in B-cell chronic lymphocytic leukemia (B-CLL). We constructed a high-resolution physical map covering the critical deleted region in B-CLL at 13q14 and flanking sequences. The order and position of both genomic markers and known genes were determined precisely. Three novel genes, CLLD6, CLLD7, and CLLD8, were isolated and characterized. The predicted protein sequence of CLLD6 revealed no homology with known proteins. However, both CLLD7 and CLLD8 predicted proteins contain known functional domains. CLLD7 has both an RCC1 and a BTB domain, and could thus be involved in cell cycle regulation by chromatin remodeling. CLLD8 contains a methyl-CpG binding, a preSET and a SET domain, suggesting that CLLD8 might be associated with methylation-mediated transcriptional repression. Mutation analysis of hematopoietic tumor cell lines and B-CLL tumor samples revealed no point mutations within the coding region of these three novel genes. The functional domains present within CLLD7 and CLLD8 suggest that the proteins may be involved in critical cellular processes such as cell cycle and transcriptional control and could therefore be directly or indirectly involved in leukemogenesis.

[1]  C. Ponting,et al.  Regulation of chromatin structure by site-specific histone H3 methyltransferases , 2000, Nature.

[2]  H. Mizoguchi,et al.  Delineation of the frequently deleted region on chromosome arm 13q in B-cell non-Hodgkin's lymphoma. , 2000, International journal of hematology.

[3]  R. Houtz,et al.  Rubisco small and large subunit N-methyltransferases. Bi- and mono-functional methyltransferases that methylate the small and large subunits of Rubisco. , 1999, The Journal of biological chemistry.

[4]  A. Yoshimura,et al.  A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins. , 1999, Biochemical and biophysical research communications.

[5]  R. Eisenman,et al.  Sin Meets NuRD and Other Tails of Repression , 1999, Cell.

[6]  A. Bird,et al.  Methylation-Induced Repression— Belts, Braces, and Chromatin , 1999, Cell.

[7]  D. Jäger,et al.  Antigens recognized by autologous antibody in patients with renal‐cell carcinoma , 1999, International journal of cancer.

[8]  M. Devilder,et al.  Exclusion of Leu1 and Leu2 genes as tumor suppressor genes in 13q14.3-deleted B-CLL , 1999, Leukemia.

[9]  Johnson M Liu,et al.  Chromatin remodeling and leukemia: new therapeutic paradigms. , 1999, Blood.

[10]  Iain W. Mattaj,et al.  Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation , 1999, Nature.

[11]  A. Wolffe,et al.  The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA. , 1999, Biochemistry.

[12]  M. Carrasquillo,et al.  Assignment of a novel bifurcated SET domain gene, SETDB1, to human chromosome band 1q21 by in situ hybridization and radiation hybrids , 1999, Cytogenetic and Genome Research.

[13]  V. Colot,et al.  Eukaryotic DNA methylation as an evolutionary device , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  G. Schotta,et al.  Functional mammalian homologues of the Drosophila PEV‐modifier Su(var)3‐9 encode centromere‐associated proteins which complex with the heterochromatin component M31 , 1999, The EMBO journal.

[15]  C. Croce.  Role of TCL1 and ALL1 in human leukemias and development. , 1999, Cancer research.

[16]  M. Devilder,et al.  cDNA cloning, gene characterization and 13q14.3 chromosomal assignment of CHC1-L, a chromosome condensation regulator-like guanine nucleotide exchange factor. , 1998, Genomics.

[17]  V. Bardwell,et al.  The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT , 1998, Oncogene.

[18]  G. Privé,et al.  Crystal structure of the BTB domain from PLZF. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  M. Devilder,et al.  Assignment of 48 ESTs to chromosome 13 band q14.3 and expression pattern for ESTs located in the core region deleted in B-CLL. , 1998, Genomics.

[20]  L. Hawthorn,et al.  Construction of a bacterial artificial chromosome (BAC) contig across the minimally deleted region in 13q14.3 in B‐cell chronic lymphocytic leukemia , 1998, Annals of human genetics.

[21]  J. Vonesch,et al.  Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators , 1998, The EMBO journal.

[22]  J. Strouboulis,et al.  Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription , 1998, Nature Genetics.

[23]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[24]  H. Lehrach,et al.  A cosmid and cDNA fine physical map of a human chromosome 13q14 region frequently lost in B‐cell chronic lymphocytic leukemia and identification of a new putative tumor suppressor gene, Leu5 , 1998, FEBS letters.

[25]  O. Rozenblatt-Rosen,et al.  The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  W. Harris,et al.  Molecular and biologic determinants of neoadjuvant chemotherapy of locoregional breast cancer. , 1998, Seminars in oncology.

[27]  Alfred Wittinghofer,et al.  The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller , 1998, Nature.

[28]  S. Inoue,et al.  Role of the histone deacetylase complex in acute promyelocytic leukaemia , 1998, Nature.

[29]  E. Zabarovsky,et al.  Detailed molecular delineation of 13q14.3 loss in B-cell chronic lymphocytic leukemia. , 1998, Blood.

[30]  G. Juliusson,et al.  Cytogenetics in chronic lymphocytic leukemia. , 1998, Seminars in oncology.

[31]  C. Croce,et al.  Sequence of the FRA3B common fragile region: implications for the mechanism of FHIT deletion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[32]  T. Shaikh,et al.  Construction of a 780-kb PAC, BAC, and cosmid contig encompassing the minimal critical deletion involved in B cell chronic lymphocytic leukemia at 13q14.3. , 1997, Genomics.

[33]  E. Zabarovsky,et al.  Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia , 1997, Oncogene.

[34]  M. Soares,et al.  Cloning and gene mapping of the chromosome 13q14 region deleted in chronic lymphocytic leukemia. , 1997, Genomics.

[35]  M. Pazin,et al.  What's Up and Down with Histone Deacetylation and Transcription? , 1997, Cell.

[36]  D. Catovsky,et al.  Interphase cytogenetics in chronic lymphocytic leukemia. , 1997, Cancer genetics and cytogenetics.

[37]  Richard S. Jones,et al.  The Drosophila Enhancer of zeste gene encodes a chromosomal protein: examination of wild-type and mutant protein distribution. , 1996, Development.

[38]  M. Caligiuri,et al.  Minimal region of loss at 13q14 in B-cell chronic lymphocytic leukemia. , 1996, Blood.

[39]  T. Nishimoto,et al.  RCC1 in the Ran pathway. , 1996, Journal of biochemistry.

[40]  M. Barbacid,et al.  p619, a giant protein related to the chromosome condensation regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab proteins. , 1996, The EMBO journal.

[41]  O. Hobert,et al.  Isolation and developmental expression analysis of Enx-1, a novel mouse Polycomb group gene , 1996, Mechanisms of Development.

[42]  E. Zabarovsky,et al.  13q deletions in lymphoid malignancies. , 1995, Blood.

[43]  H. Döhner,et al.  Heterogeneity of deletions involving RB-1 and the D13S25 locus in B-cell chronic lymphocytic leukemia revealed by fluorescence in situ hybridization. , 1995, Cancer research.

[44]  T. Gibson,et al.  The PHD finger: implications for chromatin-mediated transcriptional regulation. , 1995, Trends in biochemical sciences.

[45]  G. Privé,et al.  The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[46]  G. Reuter,et al.  The protein encoded by the Drosophila position‐effect variegation suppressor gene Su(var)3‐9 combines domains of antagonistic regulators of homeotic gene complexes. , 1994, The EMBO journal.

[47]  R. Treisman,et al.  The POZ domain: a conserved protein-protein interaction motif. , 1994, Genes & development.

[48]  D. Oscier.  Cytogenetic and molecular abnormalities in chronic lymphocytic leukaemia. , 1994, Blood reviews.

[49]  L. Hawthorn,et al.  Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia. , 1994, Oncogene.

[50]  A. Zelent,et al.  PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[51]  K Offit,et al.  Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. , 1993, Science.

[52]  A. Bird,et al.  Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. , 1993, Nucleic acids research.

[53]  L. Szekely,et al.  Chronic lymphocytic leukemia cells with allelic deletions at 13q14 commonly have one intact RB1 gene: evidence for a role of an adjacent locus. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[54]  L. Hawthorn,et al.  The consistent 13q14 translocation breakpoint seen in chronic B-cell leukaemia (BCLL) involves deletion of the D13S25 locus which lies distal to the retinoblastoma predisposition gene. , 1993, Oncogene.

[55]  E. Ranheim,et al.  Confirmation of Rb gene defects in B‐CLL clones and evidence for variable predominance of the Rb defective cells within the CLL clone , 1993, British journal of haematology.

[56]  H. Döhner,et al.  High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics , 1993 .

[57]  H. Alder,et al.  The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene , 1992, Cell.

[58]  A. Bird,et al.  Purification, sequence, and cellular localization of a novel chromosomal protein that binds to Methylated DNA , 1992, Cell.

[59]  G. Gahrton,et al.  Retinoblastoma gene deletions in b‐cell chronic lymphocytic leukemia , 1992, Genes, chromosomes & cancer.

[60]  F. Bischoff,et al.  Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1 , 1991, Nature.

[61]  K. Kuma,et al.  Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation. , 1987, Genes & development.

[62]  G. Cimino,et al.  ALL1 gene alterations in acute leukemia: biological and clinical aspects. , 1998, Haematologica.

[63]  T. Jenuwein,et al.  SET domain proteins modulate chromatin domains in eu- and heterochromatin , 1998, Cellular and Molecular Life Sciences CMLS.

[64]  H. Hishigaki,et al.  Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1. , 1997, Cytogenetics and cell genetics.

[65]  F. Ross,et al.  Evidence for a new tumour suppressor locus (DBM) in human B–cell neoplasia telomeric to the retinoblastoma gene , 1993, Nature Genetics.

[66]  A. Bird,et al.  Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins , 2022 .