A Lamin-Associated Chromatin Model for Chromosome Organization

We propose a simple model for chromatin organization based on the interaction of the chromatin fibers with lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization and hence gene expression in the cells. We provide a quantitative understanding of lamin-associated chromatin organization in a crowded macromolecular environment by systematically varying the heteropolymer segment distribution and the strength of the lamin-chromatin attractive interaction. Our minimal polymer model reproduces the formation of lamin-associated-domains and provides an in silico tool for quantifying domain length distributions for different distributions of heteropolymer segments. We show that a Gaussian distribution of heteropolymer segments, coupled with strong lamin-chromatin interactions, can qualitatively reproduce observed length distributions of lamin-associated-domains. Further, lamin-mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely packed gene-rich euchromatin regions.     

Religious Aspects of the Social Organization of a Castilian Village

The functional context of local religious practices within the structure of formal Catholicism in Spain has received little attention. Close examination of the ceremonial life of a Castilian village, and of the attitudes accompanying ceremonial and nonceremonial events, points to the existence of a complex of political and economic activities that are the chief objects of ritual sanctification and the arena in which religious sanctions function to maintain social control in the community. A survey of the ethnographic literature indicates that religious ceremonial may function in similar contexts in extended areas of the Iberian peninsula. The Castilian case and the available comparative data point to the crucial role of local religious traditions in strengthening territorial ties and in helping to define and integrate some of the fundamental units of the social structure.     

THE HUMAN CHROMOSOME : Electron Microscopic Observations on Chromatin Fiber Organization

Human lymphocytes were grown in short-term tissue culture and were arrested in metaphase with Colcemid. Their chromosomes were prepared by the Langmuir trough-critical point drying technique and were examined under the electron microscope. In addition, some chromosomes were digested with trypsin, Pronase, or DNase. The chromosomes consist entirely of tightly packed, 240 ± 50-A chromatin fibers. Trypsin and Pronase treatments induce relaxation of fiber packing and reveal certain underlying fiber arrangements. Furthermore, trypsin treatment demonstrates that the chromatin fiber has a 25–50 A trypsin-resistant core surrounded by a trypsin-sensitive sheath. DNase digestion suggests that this core contains DNA.     

Changes in Chromatin Organization during Early Development and Carcinogenesis

Similar changes in chromatin organization take place during development and carcinogenesis. The size of chromatin loop domains fixed on the nuclear skeleton (matrix) increased from 20 to approximately 200 kb. These changes are accompanied by an increased size of replicons and altered specificity of loop attachment to the nuclear matrix. During carcinogenesis, inverse changes in the chromatin structure are observed, neoplastic cells are dedifferentiated and return to the initial state. In this review, we consider new experimental data on organization of the DFNA loops and nuclear matrix in embryogenesis and carcinogenesis.     

Chromatin Immunoprecipitation Indirect Peaks Highlight Long-Range Interactions of Insulator Proteins and Pol II Pausing

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A Network Model of the Molecular Organization of Chromatin in Drosophila

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Highlights? DamID identifies 42 previously unknown chromatin proteins ? Binding maps of new and known chromatin components yield a chromatin network model ? The network model predicts functions of most of the 42 new chromatin proteins ? The chromatin protein network is functionally compartmentalized     

Native Chromatin Proteomics Reveals a Role for Specific Nucleoporins in Heterochromatin Organization and Maintenance

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Poly(ADP-ribose) Polymerase-1 (PARP-1) Contributes to the Barrier Function of a Vertebrate Chromatin Insulator

The prototypic chromatin insulator cHS4 has proven effective in reducing silencing chromosomal position effects in a variety of settings. Most of this barrier insulator activity has been mapped to a 250-bp core region, as well as to several proteins that bind this region. However, recent studies from our laboratory demonstrated that an extended 400-bp core region of the cHS4 element is necessary to achieve full barrier insulator activity when used as a single copy in the context of recombinant gammaretroviral and lentiviral vectors. In this study, electrophoretic gel mobility shift assays revealed specific DNA-protein binding activities associated with the distal portion of this extended core region. Affinity purification and tandem mass spectrometry studies led to the identification of one of these proteins as poly(ADP-ribose) polymerase-1 (PARP-1). The identity of this binding activity as PARP-1 was subsequently verified by a variety of biochemical studies in vitro and by chromatin immunoprecipitation studies in vivo. Functional studies with gammaretroviral reporter vectors in cell lines and primary mouse bone marrow progenitor cultures showed that cHS4 barrier activity was abrogated upon mutation of the putative PARP-1-binding site or upon treatment with a PARP inhibitor, respectively. The barrier activity of the cHS4 element was also found to be abrogated in studies using bone marrow from Parp1-null mice. Taken together, this study demonstrates that binding of PARP-1 plays a key functional role in the barrier activity of the extended cHS4 insulator core element.     

DNA Sequence-Directed Organization of Chromatin: Structure-Based Computational Analysis of Nucleosome-Binding Sequences

The folding of DNA on the nucleosome core particle governs many fundamental issues in eukaryotic molecular biology. In this study, an updated set of sequence-dependent empirical “energy” functions, derived from the structures of other protein-bound DNA molecules, is used to investigate the extent to which the architecture of nucleosomal DNA is dictated by its underlying sequence. The potentials are used to estimate the cost of deforming a collection of sequences known to bind or resist uptake in nucleosomes along various left-handed superhelical pathways and to deduce the features of sequence contributing to a particular structural form. The deformation scores reflect the choice of template, the deviations of structural parameters at each step of the nucleosome-bound DNA from their intrinsic values, and the sequence-dependent “deformability” of a given dimer. The correspondence between the computed scores and binding propensities points to a subtle interplay between DNA sequence and nucleosomal folding, e.g., sequences with periodically spaced pyrimidine-purine steps deform at low cost along a kinked template whereas sequences that resist deformation prefer a smoother spatial pathway. Successful prediction of the known settings of some of the best-resolved nucleosome-positioning sequences, however, requires a template with “kink-and-slide” steps like those found in high-resolution nucleosome structures.