Experimental observations of a nuclear matrix.

Nuclei are intricately structured, and nuclear metabolism has an elaborate spatial organization. The architecture of the nucleus includes two overlapping and nucleic-acid-containing structures - chromatin and a nuclear matrix. The nuclear matrix is observed by microscopy in live, fixed and extracted cells. Its ultrastructure and composition show it to be, in large part, the ribonucleoprotein (RNP) network first seen in unfractionated cells more than 30 years ago. At that time, the discovery of this RNP structure explained surprising observations that RNA, packaged in proteins, is attached to an intranuclear, non-chromatin structure. Periodic and specific attachments of chromatin fibers to the nuclear matrix create the chromatin loop domains that can be directly observed by microscopy or inferred from biochemical experiments. The ultrastructure of the nuclear matrix is well characterized and consists of a nuclear lamina and an internal nuclear network of subassemblies linked together by highly structured fibers. These complex fibers are built on an underlying scaffolding of branched 10-nm filaments that connect to the nuclear lamina. The structural proteins of the nuclear lamina have been well characterized, but the structural biochemistry of the internal nuclear matrix has received less attention. Many internal matrix proteins have been identified, but far less is known about how these proteins assemble to make the fibers, filaments and other assemblies of the internal nuclear matrix. Correcting this imbalance will require the combined application of biochemistry and electron microscopy. The central problem in trying to define nuclear matrix structure is to identify the proteins that assemble into the 10-nm filaments upon which the interior architecture of the nucleus is constructed. Only by achieving a biochemical characterization of the nuclear matrix will we advance beyond simple microscopic observations of structure to a better understanding of nuclear matrix function, regulation and post-mitotic assembly.

[1]  J. Lawrence,et al.  Seeking Common Ground in Nuclear Complexity , 2000, The Journal of cell biology.

[2]  Eric Verdin,et al.  Reduced Mobility of the Alternate Splicing Factor (Asf) through the Nucleoplasm and Steady State Speckle Compartments , 2000, The Journal of cell biology.

[3]  T Misteli,et al.  Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. , 2000, Journal of cell science.

[4]  J. Wooley,et al.  Nuclear matrix-like filaments and fibrogranular complexes form through the rearrangement of specific nuclear ribonucleoproteins. , 2000, Molecular biology of the cell.

[5]  W. Chia,et al.  The EAST protein of Drosophila controls an expandable nuclear endoskeleton , 2000, Nature Cell Biology.

[6]  H. Leonhardt,et al.  Dynamics of DNA Replication Factories in Living Cells , 2000, The Journal of cell biology.

[7]  T. Misteli,et al.  High mobility of proteins in the mammalian cell nucleus , 2000, Nature.

[8]  Carolyn L. Smith,et al.  Subnuclear Trafficking of Estrogen Receptor-α and Steroid Receptor Coactivator-1 , 2000 .

[9]  M. Cohen,et al.  Review: nuclear lamins--structural proteins with fundamental functions. , 2000, Journal of structural biology.

[10]  T. Pederson,et al.  Half a century of "the nuclear matrix". , 2000, Molecular biology of the cell.

[11]  H. Niida,et al.  The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. , 2000, Genes & development.

[12]  G. Crabtree,et al.  Searching for a function for nuclear actin. , 2000, Trends in cell biology.

[13]  J. McNally,et al.  The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. , 2000, Science.

[14]  U. Hellman,et al.  Electron Tomography Reveals Posttranscriptional Binding of Pre-Mrnps to Specific Fibers in the Nucleoplasm , 2000, The Journal of cell biology.

[15]  M. Mancini,et al.  Subnuclear trafficking of estrogen receptor-alpha and steroid receptor coactivator-1. , 2000, Molecular endocrinology.

[16]  P. Sharp,et al.  The SRm160/300 splicing coactivator subunits. , 2000, RNA.

[17]  B. O’Malley,et al.  FRAP reveals that mobility of oestrogen receptor-α is ligand- and proteasome-dependent , 2000, Nature Cell Biology.

[18]  T. Cremer,et al.  Quantitative motion analysis of subchromosomal foci in living cells using four-dimensional microscopy. , 1999, Biophysical journal.

[19]  S. Masich,et al.  The intranuclear movement of Balbiani ring premessenger ribonucleoprotein particles. , 1999, Experimental cell research.

[20]  Ronald Berezney,et al.  Three-Dimensional Visualization of Transcription Sites and Their Association with Splicing Factor–Rich Nuclear Speckles , 1999, The Journal of cell biology.

[21]  Hong Ma,et al.  Association of Chromosome Territories with the Nuclear Matrix , 1999, The Journal of cell biology.

[22]  A. F. Neuwald,et al.  Purification and biochemical characterization of interchromatin granule clusters , 1999, The EMBO journal.

[23]  P. Cook.  The organization of replication and transcription. , 1999, Science.

[24]  F. Boisvert,et al.  Direct visualization of a protein nuclear architecture. , 1999, Molecular biology of the cell.

[25]  J. Davie,et al.  Purification and characterization of chicken erythrocyte histone deacetylase 1. , 1999, Biochemistry.

[26]  M. Snyder,et al.  A Nonerythroid Isoform of Protein 4.1R Interacts with the Nuclear Mitotic Apparatus (NuMA) Protein , 1999, The Journal of cell biology.

[27]  M. Engelhardt.  Demonstration of a DNase-sensitive network associated with the nuclear pore complexes in rat liver nuclei , 1999, Chromosoma.

[28]  R. Singer,et al.  Movement of nuclear poly(A) RNA throughout the interchromatin space in living cells , 1999, Current Biology.

[29]  K Weber,et al.  Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice , 1999, The EMBO journal.

[30]  Bing Liu,et al.  Subnuclear partitioning and functional regulation of the Pit‐1 transcription factor , 1999, Journal of cellular biochemistry.

[31]  J. R. Coleman,et al.  Processing of Endogenous Pre-mRNAs in Association with SC-35 Domains Is Gene Specific , 1999, The Journal of cell biology.

[32]  G. Krockmalnic,et al.  The nuclear matrix prepared by amine modification. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. van Driel,et al.  Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. , 1999, Molecular biology of the cell.

[34]  M. Goldberg,et al.  The nuclear lamina: molecular organization and interaction with chromatin. , 1999, Critical reviews in eukaryotic gene expression.

[35]  Y. Jin,et al.  Chromatin structure and nuclear remodeling. , 1999, Critical reviews in eukaryotic gene expression.

[36]  J. Harborth,et al.  Induction of a regular nuclear lattice by overexpression of NuMA. , 1998, Experimental cell research.

[37]  E M Manders,et al.  Numbers and organization of RNA polymerases, nascent transcripts, and transcription units in HeLa nuclei. , 1998, Molecular biology of the cell.

[38]  T. Misteli,et al.  The cellular organization of gene expression. , 1998, Current opinion in cell biology.

[39]  D. E. Wolf,et al.  Intranuclear diffusion and hybridization state of oligonucleotides measured by fluorescence correlation spectroscopy in living cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. Jaenisch,et al.  RNA and the Epigenetic Regulation of X Chromosome Inactivation , 1998, Cell.

[41]  T. Kohwi-Shigematsu,et al.  The Genomic Sequences Bound to Special AT-rich Sequence-binding Protein 1 (SATB1) In Vivo in Jurkat T Cells Are Tightly Associated with the Nuclear Matrix at the Bases of the Chromatin Loops , 1998, The Journal of cell biology.

[42]  P. Sharp,et al.  A coactivator of pre-mRNA splicing. , 1998, Genes & development.

[43]  S. Fakan,et al.  Fine Structural Specific Visualization of RNA on Ultrathin Sections , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[44]  Ronald Berezney,et al.  The new paradigm: Integrating genomic function and nuclear architecture , 1998, Journal of cellular biochemistry.

[45]  B. Alberts,et al.  Two proteins that cycle asynchronously between centrosomes and nuclear structures: Drosophila CP60 and CP190. , 1997, Journal of cell science.

[46]  G. Schatten,et al.  Evidence for the Presence of Myosin I in the Nucleus* , 1997, The Journal of Biological Chemistry.

[47]  Daniel Axelrod,et al.  Chromatin Dynamics in Interphase Nuclei and Its Implications for Nuclear Structure , 1997, The Journal of cell biology.

[48]  J. Lawrence,et al.  Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Tom Misteli,et al.  The dynamics of a pre-mRNA splicing factor in living cells , 1997, Nature.

[50]  G. Krockmalnic,et al.  The nuclear matrix revealed by eluting chromatin from a cross-linked nucleus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[51]  C. Larabell,et al.  Structural Protein 4.1 in the Nucleus of Human Cells: Dynamic Rearrangements during Cell Division , 1997, The Journal of cell biology.

[52]  M. Yaniv,et al.  Components of the Human SWI/SNF Complex Are Enriched in Active Chromatin and Are Associated with the Nuclear Matrix , 1997, The Journal of cell biology.

[53]  D E Ingber,et al.  Mechanical continuity and reversible chromosome disassembly within intact genomes removed from living cells , 1997, Journal of cellular biochemistry.

[54]  D. Spector,et al.  Nuclear organization and gene expression. , 1996, Experimental cell research.

[55]  A Benner,et al.  Active and inactive genes localize preferentially in the periphery of chromosome territories , 1996, The Journal of cell biology.

[56]  R Eils,et al.  Nuclear architecture and the induction of chromosomal aberrations. , 1996, Mutation research.

[57]  T. Misteli,et al.  Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors. , 1996, Molecular biology of the cell.

[58]  B. Humbel,et al.  hnRNP proteins and B23 are the major proteins of the internal nuclear matrix of HeLa S3 cells , 1996, Journal of cellular biochemistry.

[59]  B. Nagarajan,et al.  Inhibition by quercetin and luteolin of chromosomal alterations induced by salted, deep-fried fish and mutton in rats. , 1996, Mutation research.

[60]  R. van Driel,et al.  Ultrastructural localization of active genes in nuclei of A431 cells , 1996, Journal of cellular biochemistry.

[61]  J. Mcneil,et al.  XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure , 1996, The Journal of cell biology.

[62]  A. Sasseville,et al.  Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. , 1995, Journal of cell science.

[63]  B. Blencowe,et al.  The architectural organization of nuclear metabolism. , 1995, International review of cytology.

[64]  T. Boulikas,et al.  Chromatin domains and prediction of MAR sequences. , 1995, International review of cytology.

[65]  B. Brinkley,et al.  Nuclear matrix proteins as structural and functional components of the mitotic apparatus. , 1995, International review of cytology.

[66]  H. Leonhardt,et al.  Targeting and association of proteins with functional domains in the nucleus: the insoluble solution. , 1995, International review of cytology.

[67]  S. Razin,et al.  Specificity and functional significance of DNA interaction with the nuclear matrix: new approaches to clarify the old questions. , 1995, International review of cytology.

[68]  J. Davie,et al.  The nuclear matrix and the regulation of chromatin organization and function. , 1995, International review of cytology.

[69]  P. Sharp,et al.  Association of nuclear matrix antigens with exon-containing splicing complexes , 1994, The Journal of cell biology.

[70]  J. Davie,et al.  Histone acetyltransferase is associated with the nuclear matrix. , 1994, The Journal of biological chemistry.

[71]  J. Lawrence,et al.  Dynamic changes in the higher-level chromatin organization of specific sequences revealed by in situ hybridization to nuclear halos , 1994, The Journal of cell biology.

[72]  U. De Boni,et al.  Ultrastructural localization of filamentous actin within neuronal interphase nuclei in situ. , 1994, Experimental cell research.

[73]  G. Stein,et al.  Nuclear matrix association of multiple sequence-specific DNA binding activities related to SP-1, ATF, CCAAT, C/EBP, OCT-1, and AP-1. , 1993, Biochemistry.

[74]  B. van Steensel,et al.  Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus , 1993, The Journal of cell biology.

[75]  D. Jackson,et al.  Visualization of replication factories attached to a nucleoskeleton , 1993, Cell.

[76]  Y. Kohwi,et al.  A tissue-specific MAR SAR DNA-binding protein with unusual binding site recognition , 1992, Cell.

[77]  J. Bode,et al.  Biological significance of unwinding capability of nuclear matrix-associating DNAs. , 1992, Science.

[78]  K. Pienta,et al.  Identification of nuclear matrix proteins in the cancer and normal rat prostate. , 1991, Cancer research.

[79]  S. Penman,et al.  Localization of heterogeneous nuclear ribonucleoprotein in the interphase nuclear matrix core filaments and on perichromosomal filaments at mitosis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[80]  J. Lawrence,et al.  Preservation of specific RNA distribution within the chromatin-depleted nuclear substructure demonstrated by in situ hybridization coupled with biochemical fractionation , 1991, The Journal of cell biology.

[81]  D. Jackson,et al.  Active RNA polymerase I is fixed within the nucleus of HeLa cells. , 1990, The EMBO journal.

[82]  J. Nickerson,et al.  Core filaments of the nuclear matrix , 1990, The Journal of cell biology.

[83]  D. Jackson,et al.  The size of chromatin loops in HeLa cells. , 1990, The EMBO journal.

[84]  G. Dessev.  The Nuclear Lamina , 1990 .

[85]  S. Zeitlin,et al.  Autonomous splicing and complementation of in vivo-assembled spliceosomes , 1989, The Journal of cell biology.

[86]  R Berezney,et al.  Mapping replicational sites in the eucaryotic cell nucleus , 1989, The Journal of cell biology.

[87]  J. Nickerson,et al.  Chromatin architecture and nuclear RNA. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[88]  D. Jackson,et al.  Visualization of a filamentous nucleoskeleton with a 23 nm axial repeat. , 1988, The EMBO journal.

[89]  S. Penman,et al.  Nuclear matrix proteins reflect cell type of origin in cultured human cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[90]  R. Berezney,et al.  Enhanced processivity of nuclear matrix bound DNA polymerase alpha from regenerating rat liver. , 1987, Biochemistry.

[91]  M. Bachmann,et al.  Cytochalasin B selectively releases ovalbumin mRNA precursors but not the mature ovalbumin mRNA from hen oviduct nuclear matrix. , 1987, European journal of biochemistry.

[92]  R. Berezney,et al.  Nuclear matrix-bound DNA primase. Elucidation of an RNA priming system in nuclear matrix isolated from regenerating rat liver. , 1987, The Journal of biological chemistry.

[93]  S. Zeitlin,et al.  Pre-mRNA splicing and the nuclear matrix , 1987, Molecular and cellular biology.

[94]  U. K. Laemmli,et al.  Genes and loops in 320,000 base-pairs of the Drosophila melanogaster chromosome. , 1986, Journal of molecular biology.

[95]  S. Penman,et al.  Association of RNA with the Cytoskeleton and the Nuclear Matrix , 1986, Journal of Cell Science.

[96]  K. Pienta,et al.  The role of the nuclear matrix in the organization and function of DNA. , 1986, Annual review of biophysics and biophysical chemistry.

[97]  H. Nakayasu,et al.  Association of rapidly-labelled RNAs with actin in nuclear matrix from mouse L5178Y cells. , 1985, Experimental cell research.

[98]  D. Jackson,et al.  Transcription occurs at a nucleoskeleton. , 1985, The EMBO journal.

[99]  S. Kaufmann,et al.  A subset of non-histone nuclear proteins reversibly stabilized by the sulfhydryl cross-linking reagent tetrathionate. Polypeptides of the internal nuclear matrix. , 1984, Experimental cell research.

[100]  U. K. Laemmli,et al.  Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold , 1984, Cell.

[101]  R Berezney,et al.  Spatial distribution of DNA loop attachment and replicational sites in the nuclear matrix , 1984, The Journal of cell biology.

[102]  G. Leser,et al.  Monoclonal antibodies to heterogeneous nuclear RNA-protein complexes. The core proteins comprise a conserved group of related polypeptides. , 1984, The Journal of biological chemistry.

[103]  L. Kister,et al.  Nuclear matrix and hnRNP share a common structural constituent associated with premessenger RNA. , 1983, The EMBO journal.

[104]  D. Capco,et al.  The nuclear matrix: Three-dimensional architecture and protein composition , 1982, Cell.

[105]  K. Brasch.  Fine structure and localization of the nuclear matrix in situ. , 1982, Experimental cell research.

[106]  M. Derenzini,et al.  Relationship between the fine structural organization of chromatin and nucleic acid synthesis in regenerating rat hepatocytes. , 1981, Journal of ultrastructure research.

[107]  B. Vogelstein,et al.  Supercoiled loops and eucaryotic DNA replication , 1980, Cell.

[108]  B. Walker,et al.  The release of 40S hnRNP particles by brief digestion of HeLa nuclei with micrococcal nuclease. , 1980, Nucleic acids research.

[109]  R Berezney,et al.  Fractionation of the nuclear matrix. I. Partial separation into matrix protein fibrils and a residual ribonucleoprotein fraction , 1980, The Journal of cell biology.

[110]  K. Adolph.  Organization of chromosomes in HeLa cells: isolation of histone-depleted nuclei and nuclear scaffolds. , 1980, Journal of cell science.

[111]  B. Vogelstein,et al.  A fixed site of DNA replication in eucaryotic cells , 1980, Cell.

[112]  R. Berezney.  Dynamic properties of the nuclear matrix , 1979 .

[113]  S. Penman,et al.  Heterogeneous nuclear RNA-protein fibers in chromatin-depleted nuclei , 1978, The Journal of cell biology.

[114]  J. R. Paulson,et al.  Isolation of a protein scaffold from mitotic HeLa cell chromosomes. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[115]  A. Worcel,et al.  Isolation, characterization, and structure of the folded interphase genome of Drosophila melanogaster , 1976, Cell.

[116]  P. Cook,et al.  Characterization of nuclear structures containing superhelical DNA. , 1976, Journal of cell science.

[117]  M. Derenzini,et al.  Effects of alpha-amanitine on chromatin in regenerating rat hepatocytes: a biochemical and morphologic study. , 1976, Virchows Archiv. B, Cell pathology.

[118]  P. Cook,et al.  Supercoils in human DNA. , 1975, Journal of cell science.

[119]  J. Bachellerie,et al.  Ultrastructural organization and biochemical characterization of chromatin - RNA - protein complexes isolated from mammalian cell nuclei. , 1975, European journal of biochemistry.

[120]  I. Faiferman,et al.  Isolation of a nuclear ribonucleoprotein network that contains heterogeneous RNA and is bound to the nuclear envelope. , 1975, Biochemistry.

[121]  R Berezney,et al.  Identification of a nuclear protein matrix. , 1974, Biochemical and biophysical research communications.

[122]  W. Bernhard.  A new staining procedure for electron microscopical cytology. , 1969, Journal of ultrastructure research.

[123]  A. Monneron,et al.  Fine structural organization of the interphase nucleus in some mammalian cells. , 1969, Journal of ultrastructure research.

[124]  J. Molnár,et al.  Structural organization of nuclear complexes containing DNA-like RNA. , 1968, Journal of molecular biology.

[125]  K. Smetana,et al.  Ultrastructural aspects of the ribonucleo-protein network in nuclei of Walker tumor and rat liver. , 1967, Experimental cell research.

[126]  Watt,et al.  Journal of Cell Science , 1996, Nature.

[127]  E. Benditt.  The Cell: Its Organelles and Inclusions , 1966 .

[128]  D. Fawcett.  The cell, its organelles and inclusions : an atlas of fine structure , 1966 .

[129]  K. Smetana,et al.  A nuclear ribonucleoprotein network , 1963 .