The many roles of the transcriptional regulator CTCF.

The nuclear factor CTCF was first identified as one of the factors binding to the regulatory regions of the c-myc gene. Further study of this protein revealed roles in transcriptional repression, insulator function, and imprinting genetic information. Recent studies have provided new insight into the mechanism through which this factor acts at various levels of gene regulation.

[1]  P. Neiman,et al.  Functional Phosphorylation Sites in the C-Terminal Region of the Multivalent Multifunctional Transcriptional Factor CTCF , 2001, Molecular and Cellular Biology.

[2]  B. Liang,et al.  Transforming growth factor-β-induced transcription of the Alzheimer β-amyloid precursor protein gene involves interaction between the CTCF-complex and Smads , 2002 .

[3]  P. Schedl,et al.  The Zw5 protein, a component of the scs chromatin domain boundary, is able to block enhancer-promoter interaction. , 1999, Genes & development.

[4]  C. Kanduri,et al.  CpG methylation regulates the Igf2/H19 insulator , 2001, Current Biology.

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

[6]  R Ohlsson,et al.  CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. , 2001, Trends in genetics : TIG.

[7]  Helen Zhao,et al.  The insulator binding protein CTCF associates with the nuclear matrix. , 2003, Experimental cell research.

[8]  S. Murphy,et al.  Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. , 2000, Genome research.

[9]  G. Felsenfeld,et al.  Stopped at the border: boundaries and insulators. , 1999, Current opinion in genetics & development.

[10]  A. Wolffe,et al.  Transcriptional control: Imprinting insulation , 2000, Current Biology.

[11]  R. DePinho Transcriptional repression: The cancer-chromatin connection , 1998, Nature.

[12]  P. Shen,et al.  Effects of cis arrangement of chromatin insulators on enhancer-blocking activity. , 2001, Science.

[13]  B. Tycko,et al.  Chromosome arm 16q in Wilms tumors: Unbalanced chromosomal translocations, loss of heterozygosity, and assessment of the CTCF gene , 2002, Genes, chromosomes & cancer.

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

[15]  Ulrich K Laemmli,et al.  Structural and dynamic functions establish chromatin domains. , 2003, Molecular cell.

[16]  V. Pirrotta,et al.  Loss of insulator activity by paired Su(Hw) chromatin insulators. , 2001, Science.

[17]  A. E. Sippel,et al.  Dynamic chromatin: The regulatory domain organization of eukaryotic gene loci , 1991, Journal of cellular biochemistry.

[18]  M. Simm,et al.  Microarray analysis of differentially expressed genes in cells resistant to HIV-1. , 2004, Immunology letters.

[19]  A. Feinberg,et al.  Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. , 2002, Cancer research.

[20]  A. Vostrov,et al.  A Region to the N-terminal Side of the CTCF Zinc Finger Domain Is Essential for Activating Transcription from the Amyloid Precursor Protein Promoter* , 2002, The Journal of Biological Chemistry.

[21]  A. West,et al.  Insulators: many functions, many mechanisms. , 2002, Genes & development.

[22]  P. Neiman,et al.  CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms , 1993, Molecular and cellular biology.

[23]  G. Glenner,et al.  Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. , 1984, Biochemical and biophysical research communications.

[24]  K. Grzeschik,et al.  The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor , 1987, Nature.

[25]  M. Bartolomei,et al.  A 5' differentially methylated sequence and the 3'-flanking region are necessary for H19 transgene imprinting , 1997, Molecular and cellular biology.

[26]  W. Quitschke Two nuclear factor binding domains activate expression from the human amyloid beta-protein precursor promoter. , 1994, The Journal of biological chemistry.

[27]  Shirley M. Tilghman,et al.  CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus , 2000, Nature.

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

[29]  S. Tilghman The Sins of the Fathers and Mothers Genomic Imprinting in Mammalian Development , 1999, Cell.

[30]  K. Zhao,et al.  Visualization of chromosomal domains with boundary element-associated factor BEAF-32 , 1995, Cell.

[31]  D. Mann,et al.  The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease , 2004, Acta Neuropathologica.

[32]  D. J. Driscoll,et al.  Imprinting-mutation mechanisms in Prader-Willi syndrome. , 1999, American journal of human genetics.

[33]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

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

[35]  T. Kouzarides,et al.  Transcriptional repression by the insulator protein CTCF involves histone deacetylases. , 2000, Nucleic acids research.

[36]  A. Wolffe,et al.  The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylation. , 2002, Genes & development.

[37]  R. Weinberg Tumor suppressor genes , 1993, Neuron.

[38]  Victor V Lobanenkov,et al.  Molecular weight abnormalities of the CTCF transcription factor: CTCF migrates aberrantly in SDS-PAGE and the size of the expressed protein is affected by the UTRs and sequences within the coding region of the CTCF gene. , 1997, Nucleic acids research.

[39]  A. Ferguson-Smith,et al.  Comparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region. , 2001, Genome research.

[40]  R. Renkawitz,et al.  NeP1. A ubiquitous transcription factor synergizes with v-ERBA in transcriptional silencing. , 1993, Journal of molecular biology.

[41]  Victor V Lobanenkov,et al.  Negative protein 1, which is required for function of the chicken lysozyme gene silencer in conjunction with hormone receptors, is identical to the multivalent zinc finger repressor CTCF , 1997, Molecular and cellular biology.

[42]  C. Kanduri,et al.  The 5′ flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer–promoter communication , 2000, Current Biology.

[43]  J. Chernak,et al.  Structural features of the 5' upstream regulatory region of the gene encoding rat amyloid precursor protein. , 1993, Gene.

[44]  W. Hillen,et al.  A short autonomous repression motif is located within the N‐terminal domain of CTCF , 2004, FEBS letters.

[45]  C. Kanduri,et al.  A Differentially Methylated Imprinting Control Region within the Kcnq1 Locus Harbors a Methylation-sensitive Chromatin Insulator* , 2002, The Journal of Biological Chemistry.

[46]  A. West,et al.  Structural and functional conservation at the boundaries of the chicken β‐globin domain , 2000 .

[47]  Victor V Lobanenkov,et al.  Thyroid hormone‐regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor , 2003, The EMBO journal.

[48]  R. Renkawitz,et al.  Modular structure of a chicken lysozyme silencer: Involvement of an unusual thyroid hormone receptor binding site , 1990, Cell.

[49]  Victor V Lobanenkov,et al.  The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. , 2002, Seminars in cancer biology.

[50]  L. Chin,et al.  Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression , 1997, nature.

[51]  P. Neiman,et al.  An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes , 1996, Molecular and cellular biology.

[52]  R. Fournier,et al.  The 5' boundary of the human apolipoprotein B chromatin domain in intestinal cells. , 2001, Biochemistry.

[53]  F. Dequiedt,et al.  Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR. , 2002, Molecular cell.

[54]  A. Vostrov,et al.  The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation. , 1997, The Journal of biological chemistry.

[55]  P. Neiman,et al.  A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers , 1998, Genes, chromosomes & cancer.

[56]  Jeannie T. Lee,et al.  CTCF, a Candidate Trans-Acting Factor for X-Inactivation Choice , 2001, Science.

[57]  R. Ehrlich,et al.  Synthesis and Turnover of β2-Microglobulin in Ad12-transformed Cells Defective in Assembly and Transport of Class I Major Histocompatibility Complex Molecules* , 1997, The Journal of Biological Chemistry.

[58]  Victor V Lobanenkov,et al.  A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5'-flanking sequence of the chicken c-myc gene. , 1990, Oncogene.

[59]  M. Hattori,et al.  Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse. , 1992, Gene.

[60]  A. Levine The tumor suppressor genes. , 1993, Annual review of biochemistry.

[61]  R. Kelley,et al.  The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA-binding protein. , 1988, Genes & development.

[62]  B. Howard,et al.  A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A , 1996, Nature.

[63]  Jun Qin,et al.  Purification and functional characterization of the human N‐CoR complex: the roles of HDAC3, TBL1 and TBLR1 , 2003, The EMBO journal.

[64]  J. J. Breen,et al.  BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma , 2002, Proceedings of the National Academy of Sciences of the United States of America.