Keeping fingers crossed: heterochromatin spreading through interdigitation of nucleosome arrays

Interphase eukaryotic nuclei contain diffuse euchromatin and condensed heterochromatin. Current textbook models suggest that chromatin condensation occurs via accordion‐type compaction of nucleosome zigzag chains. Recent studies have revealed several structural aspects that distinguish the highly compact state of condensed heterochromatin. These include an extensive lateral self‐association of chromatin fibers, prominent nucleosome linker ‘stems’, and special protein factors that promote chromatin self‐association. Here I review the molecular and structural determinants of chromatin compaction and discuss how heterochromatin spreading may be mediated by lateral self‐association of zigzag nucleosome arrays.

[1]  Jordanka Zlatanova,et al.  Chromatin fibers, one-at-a-time. , 2003, Journal of molecular biology.

[2]  J. Daban.  Physical constraints in the condensation of eukaryotic chromosomes. Local concentration of DNA versus linear packing ratio in higher order chromatin structures. , 2000, Biochemistry.

[3]  J. Dubochet,et al.  Bilayers of nucleosome core particles. , 2001, Biophysical journal.

[4]  A J Koster,et al.  Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  N. Chandra,et al.  Molecular modeling of the chromatosome particle. , 2003, Nucleic acids research.

[6]  A. Sivolob,et al.  Linker histone-dependent organization and dynamics of nucleosome entry/exit DNAs. , 2003, Journal of molecular biology.

[7]  S. Henikoff,et al.  Distinct HP1 and Su(var)3-9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location. , 2003, Genes & development.

[8]  N. Huskisson,et al.  Chromatin complexes as aperiodic microcrystalline arrays that regulate genome organisation and expression. , 1998, Developmental genetics.

[9]  J. Langowski,et al.  Computer simulation of the 30-nanometer chromatin fiber. , 2002, Biophysical journal.

[10]  R. Meehan,et al.  HP1 binding to native chromatin in vitro is determined by the hinge region and not by the chromodomain , 2003, The EMBO journal.

[11]  C. Woodcock,et al.  Chromatin organization re-viewed. , 1995, Trends in cell biology.

[12]  T. Richmond,et al.  The structure of DNA in the nucleosome core , 2003, Nature.

[13]  S. Grigoryev,et al.  A chromatin folding model that incorporates linker variability generates fibers resembling the native structures. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[14]  James Allan,et al.  Formation of facultative heterochromatin in the absence of HP1 , 2003, The EMBO journal.

[15]  K. V. van Holde,et al.  Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Andrew J. Bannister,et al.  Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain , 2001, Nature.

[17]  J. Bednar,et al.  MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member* , 1999, The Journal of Biological Chemistry.

[18]  Prim B. Singh,et al.  HP1: facts, open questions, and speculation. , 2002, Journal of structural biology.

[19]  David T. Brown.  Histone H1 and the dynamic regulation of chromatin function. , 2003, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[20]  Y. Ono,et al.  Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1foo in nuclear transfer. , 2004, Developmental biology.

[21]  D. Timm,et al.  Asymmetries in the nucleosome core particle at 2.5 A resolution. , 2000, Acta crystallographica. Section D, Biological crystallography.

[22]  D. Moazed,et al.  Heterochromatin and Epigenetic Control of Gene Expression , 2003, Science.

[23]  J. Dubochet,et al.  Chromatin conformation and salt-induced compaction: three-dimensional structural information from cryoelectron microscopy , 1995, The Journal of cell biology.

[24]  R. Schneiter,et al.  Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine biosynthetic machinery with the prohibitin complex of Saccharomyces cerevisiae. , 2003, Molecular biology of the cell.

[25]  V. Ramakrishnan,et al.  Position and orientation of the globular domain of linker histone H5 on the nucleosome , 1998, Nature.

[26]  Songtao Jia,et al.  RNAi-Mediated Targeting of Heterochromatin by the RITS Complex , 2004, Science.

[27]  K. V. van Holde,et al.  Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Bird,et al.  MeCP2 Repression Goes Nonglobal , 2003, Science.

[29]  Tom Misteli,et al.  Maintenance of Stable Heterochromatin Domains by Dynamic HP1 Binding , 2003, Science.

[30]  S. Elgin,et al.  Position effect variegation in Drosophila is associated with an altered chromatin structure. , 1995, Genes & development.

[31]  J. Whisstock,et al.  Role of the M-loop and Reactive Center Loop Domains in the Folding and Bridging of Nucleosome Arrays by MENT* , 2003, Journal of Biological Chemistry.

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

[33]  Hiten D. Madhani,et al.  Conserved Histone Variant H2A.Z Protects Euchromatin from the Ectopic Spread of Silent Heterochromatin , 2003, Cell.

[34]  P. Collas.  Nuclear reprogramming in cell-free extracts. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[35]  D. Kioussis,et al.  Modulation of Heterochromatin Protein 1 Dynamics in Primary Mammalian Cells , 2003, Science.

[36]  Rachel A. Horowitz-Scherer,et al.  Chromatin Compaction by Human MeCP2 , 2003, Journal of Biological Chemistry.

[37]  Dirk Schübeler,et al.  Nuclear compartmentalization and gene activity , 2000, Nature Reviews Molecular Cell Biology.

[38]  T. Kohwi-Shigematsu,et al.  Tissue-specific nuclear architecture and gene expession regulated by SATB1 , 2003, Nature Genetics.

[39]  M. Koury,et al.  Morphological changes in erythroblasts during erythropoietin-induced terminal differentiation in vitro. , 1988, Experimental hematology.

[40]  Karl Mechtler,et al.  Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins , 2001, Nature.

[41]  S. Grigoryev,et al.  Loosened nucleosome linker folding in transcriptionally active chromatin of chicken embryo erythrocyte nuclei. , 1990, Nucleic acids research.

[42]  S. Jacobs,et al.  Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail , 2002, Science.

[43]  J. Hansen,et al.  Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions. , 2002, Annual review of biophysics and biomolecular structure.

[44]  N. Chandra,et al.  Prediction of an HMG‐box fold in the C‐terminal domain of histone H1: Insights into its role in DNA condensation , 2002, Proteins.

[45]  James A. Birchler,et al.  Heterochromatic Silencing and HP1 Localization in Drosophila Are Dependent on the RNAi Machinery , 2004, Science.

[46]  J. Daban.  High concentration of DNA in condensed chromatin. , 2003, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[47]  S. Elgin,et al.  Epigenetic Codes for Heterochromatin Formation and Silencing Rounding up the Usual Suspects , 2002, Cell.

[48]  A Klug,et al.  Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin , 1979, The Journal of cell biology.

[49]  K. Luger,et al.  Crystal structure of a nucleosome core particle containing the variant histone H2A.Z , 2000, Nature Structural Biology.

[50]  D A Agard,et al.  The three-dimensional architecture of chromatin in situ: electron tomography reveals fibers composed of a continuously variable zig-zag nucleosomal ribbon , 1994, The Journal of cell biology.

[51]  K. Luger,et al.  The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states , 2002, Nature Structural Biology.

[52]  A. Belmont,et al.  Engineered chromosome regions with altered sequence composition demonstrate hierarchical large-scale folding within metaphase chromosomes , 2003, The Journal of cell biology.

[53]  H. Weintraub.  Histone-h1-dependent chromatin superstructures and the suppression of gene activity , 1984, Cell.

[54]  V. Ramakrishnan,et al.  Chromatin higher-order structure studied by neutron scattering and scanning transmission electron microscopy. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[55]  S. Grigoryev,et al.  Insulation of the Chicken β-Globin Chromosomal Domain from a Chromatin-Condensing Protein, MENT , 2003, Molecular and Cellular Biology.

[56]  V. Ramakrishnan,et al.  Linker histone-dependent DNA structure in linear mononucleosomes. , 1996, Journal of molecular biology.

[57]  N. Gilbert,et al.  Distinctive higher-order chromatin structure at mammalian centromeres , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[58]  J. Whisstock,et al.  Inhibitory Activity of a Heterochromatin-associated Serpin (MENT) against Papain-like Cysteine Proteinases Affects Chromatin Structure and Blocks Cell Proliferation* , 2002, Journal of Biological Chemistry.

[59]  Karolin Luger,et al.  Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions , 2001, The EMBO journal.

[60]  C. Bustamante,et al.  Pulling chromatin fibers: computer simulations of direct physical micromanipulations. , 2000, Journal of molecular biology.

[61]  J. Widom.  Physicochemical studies of the folding of the 100 A nucleosome filament into the 300 A filament. Cation dependence. , 1986, Journal of molecular biology.

[62]  D. W. Abbott,et al.  Characterization of the Stability and Folding of H2A.Z Chromatin Particles , 2001, The Journal of Biological Chemistry.

[63]  L. Wallrath,et al.  Effects of tethering HP1 to euchromatic regions of the Drosophila genome , 2003, Development.

[64]  V. Ramakrishnan,et al.  Identification of two DNA‐binding sites on the globular domain of histone H5. , 1996, The EMBO journal.

[65]  G. Sudlow,et al.  Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain , 1999, The Journal of cell biology.

[66]  C. Bustamante,et al.  Pulling a single chromatin fiber reveals the forces that maintain its higher-order structure. , 2000, Proceedings of the National Academy of Sciences of the United States of America.