ISSN:0730-2312    

DOI:10.1002/jcb.240550102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractDuring the past several years it has become increasingly evident that the three‐dimensional organization of the nucleus plays a critical role in transcriptional control. The principal theme of this prospect will be the contribution of nuclear structure to the regulation of gene expression as functionally related to development and maintenance of the osteoblast phenotype during establishment of bone tissue‐like organization. The contributions of nuclear structure as it regulates and is regulated by the progressive developmental expression of cell growth and bone cell related genes will be examined. We will consider signalling mechanisms that integrate the complex and interdependent responsiveness to physiological mediators of osteoblast proliferation and differentiation. The focus will be on the involvement of the nuclear matrix, chromatin structure, and nucleosome organization in transcriptional control of cell growth and bone cell related genes. Findings are presented which are consistent with involvement of nuclear structure in gene regulatory mechanisms which support osteoblast differentiation by addressing four principal questions: (1) Does the representation of nuclear matrix proteins reflect the developmental stage‐specific requirements for modifications in transcription during osteoblast differentiation? (2) Are developmental stage‐specific transcription factors components of nuclear matrix proteins? (3) Can the nuclear matrix facilitate interrelationships between physiological regulatory signals that control transcription and the integration of activities of multiple promoter regulatory elements? (4) Are alterations in gene expression and cell phenotypic properties in transformed osteoblasts and osteosarcoma cells reflected by modifications in nuclear matrix proteins? There is a striking representation of nuclear matrix proteins unique to cells, tissues as well as developmental stages of differentiation, and tissue organization. Together with selective association of regulatory molecules with the nuclear matrix in a growth and differentiation‐specific manner, there is a potential for application of nuclear matrix proteins in tumor diagnosis, assessment of tumor progression, and prognosis of therapies where properties of the transformed state of cells is modified. It is realistic to consider the utilization of nuclear matrix proteins for targeting regions of cell nuclei and specific genomic domains on the basis of developmental phenotypic properties or tissue pathology. © 1994 Wiley

ISSN:0730-2312    

DOI:10.1002/jcb.240550103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe fact that cells make directed decisions regarding how to use energy, i.e., where to direct intracellular particles or where to move, suggests that energy can be, and is, harnessed in specific ways. It is now well established that the chemical reactions of the cell do not occur in nonorganized soup, but rather in the context of ordered structure. The physical components that make up this ordered structure of the cell are part of the tissue matrix, which consists of the dynamic linkages between the skeletal networks of the nucleus (the nuclear matrix), the cytoplasm (the cytoskeleton), and the extracellular environment (the extracellular matrix). To understand gene function and how the energy of the cell is directed towards accomplishing the tasks directed by DNA (gene expression), a further understanding of how cell structure is tied to cellular energy and function is required. We propose that the structural components of the cell harness cellular energy to direct cell functions by providing a dynamic bridge between thermodynamics and gene expression. © 1994 Wiley‐Liss, I

ISSN:0730-2312    

DOI:10.1002/jcb.240550104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractTissue specific regulation of gene expression by a single transcription factor or group of transcription factors cannot be explained simply by DNA sequence alone. For example, in the same animal a particular transcription factor is capable of interacting with DNA in the nucleus of many different cell types, resulting in unique gene expressions despite the presence of a similar genome in all cells. Historically, these differences in response to a single type of factor within target tissues in the same animal have been suggested to occur through different alterations in chromatin structure. Recent, data has demonstrated that combination of hormones and transcription factors working together may cooperatively play a role in the regulation of gene expression [Pearce and Yamamoto (1993): Science 259:1161–1165]. However, the molecular mechanisms of this tissue specific regulation of gene expression still remains largely unexplained. Current evidence suggests that in different cell types the interplay between the specific three‐dimensional organization of the genome and the structural components of the nucleus, the nuclear matrix, may accomplish the regulation of specific gene expression. © 1994 Wiley‐Lis

ISSN:0730-2312    

DOI:10.1002/jcb.240550105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe have recognized about ten distinct forms of strongly basic hexapeptides, containing at least four arginines and lysines, characteristic of nuclear proteins among all eukaryotic species, including yeast, plants, flies and mammals. These basic hexapeptides are considered to be different versions of a core nuclear localization signal, NLS. Core NLSs are present in nearly all nuclear proteins and absent from nearly all “nonassociated” cytoplasmic proteins that have been investigated. We suggest that the few (∼ 10%) protein factors lacking a typical NLS core peptide may enter the nucleus via their strong crosscomplexation with their protein factor partners that possess a core NLS. Those cytoplasmic proteins found to possess a NLS‐like peptide are either tightly associated with cell membrane proteins or are integral components of large cytoplasmic protein complexes. On the other hand, some versions of core NLSs are found in many cell membrane proteins and secreted proteins. It is hypothesized that in these cases the N‐terminal hydrophobic signal peptide of extracellular proteins and the internal hydrophobic domains of transmembrane proteins are stronger determinants for their subcellular localization. The position of core NLSs among homologous nuclear proteins may or may not be conserved; however, if lost from an homolgous site it appears elsewhere in the protein.This search provides a set of rules to our understanding of the nature of core nuclear localization signals: (1) Core NLS are proposed to consist most frequently of an hexapeptide with 4 arginines and lysines; (2) aspartic and glutamic acid residues as well as bulky amino acids (F, Y, W) need not to be present in this hexapeptide; (3) acidic residues and proline or glycine that break the α‐helix are frequently in the flanking region of this hexapeptide stretch; (4) hydrophobic residues ought not to be present in the core NLS flanking region allowing for the NLS to be exposed on the protein. In this study we attempt to classify putative core NLS from a wealth of nuclear protein transcription factors from diverse species into several categories, and we propose additional core NLS structures yet to be experimentally verified. © 1994 Wi

ISSN:0730-2312    

DOI:10.1002/jcb.240550106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn mice, the first round of DNA replication occurs in fertilized eggs (1‐cell embryos), while the onset of zygotic gene transcription begins ∼ 20 hours after fertilization, a time that normally coincides with formation of a 2‐cell embryo. One approach to investigating the mechanisms that control these developmentally regulated events has been to microinject plasmid DNA into the nuclei of mouse oocytes and embryos in order to determine the requirements for unique DNA sequences that regulate transcription and replication. The results from these and other studies have revealed two important mechanisms that regulate the beginning of animal development. The first is a time dependent “zygotic clock” of unknown detail that delays the onset of transcription, regardless of whether or not a 2‐cell embryo is formed. The second is a mechanism that represses the activity of promoters and origins of replication specifically in maternal pronuclei of oocytes and 1‐cell embryos, and in all nuclei of 2‐cell embryos, regardless of their parental origin or ploidy. This repression is linked to chromatin, but the striking ability to relieve this repression with specific embryo‐responsive enhancers first appears with formation of a 2‐cell embryo. The need for a TATA‐box to mediate enhancer stimulation of promoter activity appears even later when cell differention becomes evident. Thus, a biological clock delays transcription until both paternal and maternal genomes are replicated and remodeled from a post‐meiotic state to one in which transcription is repressed by chromatin structure in a manner that can be relieved by cell‐specific enhancers at appropriate times during developmen

ISSN:0730-2312    

DOI:10.1002/jcb.240550107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the age of “virtual reality,” the imperfect microscopic silhouettes of cells and organelles are gradually being replaced by calligraphic computer drawings. In this context, textbooks and introductory slides often depict the cell nucleus as a smooth‐shaped, featureless object. However, in reality, the nuclei of different cells possess distinct sizes and morphological features which develop in a programmed fashion as each cell differentiates. To dissect this complex morphogenetic process, we need to identify the basic elements that determine nuclear architecture and the regulatory factors involved. Recently, clues about the identity of these components have been obtained both by systematic analysis and by serendipity. This review summarizes a few recent findings and ideas that may serve as a first forum for future discussions and, I hope, for further work on this topic. © 1994 Wiley‐L

ISSN:0730-2312    

DOI:10.1002/jcb.240550108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe tertiary structure of the DNA that makes up the eukaryotic genome is remarkably plastic, taking many different forms in response to the different needs of the cell. During the cell cycle of one cell, the DNA is replicated, reorganized into mitotic chromosomes, and decondensed into interphase chromatin. Within one cell at any given point in time, the chromatin is divided into hetero‐ and euchromatin reflecting active and inactive states of the DNA. This organization varies within one organism since different parts of the genome are active in different cell types. This article focuses on the most dramatic cell‐type‐specific DNA organization, that found in spermatozoa, in which the entire genome is reorganized into an inactive state that is more highly condensed than mitotic chromosomes. This unique example of eukaryotic DNA organization offers some interesting clues to the still unanswered questions about the role that the three‐dimensional packaging of DNA plays in its function. © 1994 Wiley

ISSN:0730-2312    

DOI:10.1002/jcb.240550109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractRecent genetic and biochemical studies have revealed critical information concerning the role of nucleosomes in eukaryotic gene regulation. Nucleosomes package DNA into a dynamic chromatin structure, and by assuming defined positions in chromatin, influence gene regulation. Nucleosomes can serve as repressors, presumably by blocking access to regulatory elements; consequently, the positions of nucleosomes relative to the location of cis‐acting elements are critical. Some genes have a chromatin structure that is “preset,” ready for activation, while others require “remodeling” for activation. Nucleosome positioning may be determined by multiple factors, including histone–DNA interactions, boundaries defined by DNA structure or protein binding, and higher‐order chromatin structure. © 1994 W

ISSN:0730-2312    

DOI:10.1002/jcb.240550110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractInformation in DNA is not limited to sequence information. Both local and global conformational parameters are pivotal to the interaction with a number of relevant proteins. The function of the major components of the transcription machinery (RNA polymerase II, DNA topoisomerase I, nucleosomes, the TATA‐binding factor) is dependent on the topological status of the substrate DNA molecule. The topological requirements and the conformational consensus that dictate the rules for localization of nucleosomes and define the active sites for DNA topoisomerase I have been established; the reaction of DNA topoisomerase I is regulated by a topological feedback mechanism. The integrating function of the free energy of supercoiling in the transcription process and the regulatory role of DNA topoisomerase I are discussed. © 1994 Wiley‐Liss,

ISSN:0730-2312    

DOI:10.1002/jcb.240550111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY