Chromatin assembled in the presence of cytosine arabinoside has a short nucleosome repeat

Leffak, I.M.

doi:10.1093/nar/11.16.5451

Cited by 20 publications

(9 citation statements)

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“…This indicates that the specific cell states or lineage may still require mitosis and therefore that possible stable chromatin structures may yet be important even for myoblast differentiation. Finally, ara-C and other inhibitors of DNA synthesis have differential effects on specific DNA replication origins, such as the DHFR replicon, which is relatively insensitive to inhibition and may still be reassembled into new chromatin in the presence of inhibitors (46,209,210). Altered chromatin assembly during inhibition of DNA synthesis has been reported (209,211).…”

Section: Results Which Appear To Refute Replication-based Differentiamentioning

confidence: 99%

“…Second, terminal replication, like endoreduplication, may be insensitive to (and possibly induced by) the usual inhibitors of DNA replication and may involve a DNA polymerase other than polymerase alpha. Even if these drugs inhibit completion of terminal replication, they do not appear to prevent the initiation of DNA replication, since some origins of replication can be labeled in their presence (121) and can allow the reassembly of new histones onto cis-acting regulatory regions of DNA (121,209,211). Also, because terminal replication is proposed to be the first committed event of terminal differentiation, it could be missed if not specifically sought.…”

Section: Inapparent Terminal Replication In Vertebratesmentioning

confidence: 99%

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Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

Villarreal

1991

Microbiological Reviews

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Promoter Occlusion by Nucleosomes and Other Chromatin Proteins Occlusion of promoters by bound nucleosomes also appears to be stable in vitro and refractory to factor competition (377; for reviews, see references 138 and 395). Stable DNA-bound nucleosomes are reported not to be displaced by high-affinity DNA-binding molecules such as heparin (295), nuclear factor 1 (NF1) (62), the glucocorticoid receptor (288), or the general transcription factor TFIID (400). There is a general consensus that nucleosomes will prevent

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Section: Results Which Appear To Refute Replication-based Differentiamentioning

confidence: 99%

Section: Inapparent Terminal Replication In Vertebratesmentioning

confidence: 99%

Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

Villarreal

1991

Microbiological Reviews

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“…It has been observed that reduction in the replication rate can reduce nucleosome spacing (29). Therefore, more slowly replicating regions of the genome might accumulate a higher density of nucleosomes.…”

Section: Discussionmentioning

confidence: 99%

Conserved nucleoprotein structure at the ends of vertebrate and invertebrate chromosomes.

Lejnine

Макаров

Langmore

1995

Proc. Natl. Acad. Sci. U.S.A.

155

127

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Eukaryotic chromosomes terminate with telomeres, nucleoprotein structures that are essential for chromosome stability. Vertebrate nucleosomes. Gel electrophoresis of nucleoproteins indicated that telomere core particles did not bind histone Hi, yet sedimentation analysis showed that the mononucleosomes and oligonucleosomes of telomere and bulk chromatin cosediment at low ionic strength and are sensitive to removal of Hi. Several of these experiments have been replicated with human and mouse cell lines, giving the same results (13).Studies of the origin and nature of these telomere-specific nucleosomes might give insight into the general process of nucleosome assembly and into the roles of telomeres in chromosome stability and cellular senescence. In this paper we address the question of telomere DNA and nucleoprotein structure in organisms representing the vertebrate classes Mammalia, Reptilia, Aves, Amphibia, and Pisces, as well as the invertebrate class Echinodea. The results support the hypothesis that animal cells have highly conserved telomere DNA sequences of (TTAGGG), organized largely into short nucleosomes of variable length, usually "40 bp less than nucleosomes of bulk chromatin. In addition, the distinctness of the nucleosomal ladder appears to be correlated with the length of the telomere tracts, suggesting that short telomeres might be less homogeneous than long telomeres.Telomeres are functionally and structurally distinct structures at the ends of eukaryotic chromosomes that are essential for chromosome stability and also seem important for the expression of adjacent genes, spatial arrangement of chromosomes in nuclei, and initiation of chromosome pairing during meiosis (1, 2). In protozoa and fungi the telomere DNA tracts are very short (18-600 bp), contain a 3' G-rich single-stranded tail, and are bound to nonhistone proteins, in contrast to the rest of the genome, in which the DNA and histone proteins are organized into nucleosome arrays (3). The telomeres of animals and plants are substantially longer (2-100 kb) and less well characterized (4-7). The length of telomeres from human somatic cells is directly related to the mitotic history of the cells, with an average shortening of '100 bp per division (8, 9). As telomeres reach a critical length, chromosomes seem to become unstable (10). Only immortal cells from lower eukaryotes and germline and tumor cells from higher eukaryotes have telomeres of constant length, apparently stabilized by the enzyme telomerase, which is able to add telomere sequences to the 3' termini (11).We recently characterized the nucleoprotein structure of rat telomeres by nuclease and sedimentation analyses (12). Micrococcal nuclease (MNase) studies revealed very regular arrays of nucleosomes spaced by 157 bp on the telomeres, representing the shortest nucleosomes found in animals and plants. DNase I digestion patterns and electrophoretic mobilities of the telomere nucleosomes were identical to those of bulk chromatin, suggesting that the protein composition of...

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“…Comparable results were obtained over a range of hydroxyurea doses from 3 to 20 mM. Incorporation was ended by lysis of the cells in 0.5% sodium dodecyl sulfate (SDS), digestion with proteinase K, and quantitation of 10% trichloroacetic acid precipitable radioactivity (Leffak, 1983a).…”

Section: Methodsmentioning

confidence: 87%

Nonrandom assembly of chromatin during hydroxyurea inhibition of DNA synthesis

Leffak

1988

Biochemistry

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Incubation of MSB-1 chicken lymphoblastoid cells with hydroxyurea leads to a rapid 25-fold decrease in the incorporation of [3H]thymidine into DNA and a 5-fold decrease [3H]lysine into the nucleosome core histones. I have investigated whether the distortion in the normal proportion of histone-DNA synthesis results in alterations in the nucleosome assembly process and find that neither the stoichiometry of new histone synthesis nor the deposition is appreciably changed during hydroxyurea incubation. Protein cross-linking and micrococcal nuclease digestion show that the histones synthesized during hydroxyurea treatment form octamer structures and are assembled into typical nucleosome particles. Minor nucleosome subpopulations are found which exhibit altered sensitivity to nuclease digestion and which are depleted in new histones H3 and H4. When MSB-1 cells incubated in hydroxyurea are pulsed briefly with density-labeled amino acids and [3H]lysine, the radiolabeled core histone octamers formed are as dense as individual monomer histones. These results suggest that the newly synthesized histone octamers are uniformly dense and do not contain mixtures of new and old histones. Thus, histones synthesized during hydroxyurea incubation are deposited nonrandomly and do not exchange with preexisting histones.

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Chromatin assembled in the presence of cytosine arabinoside has a short nucleosome repeat

Cited by 20 publications

References 53 publications

Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

Conserved nucleoprotein structure at the ends of vertebrate and invertebrate chromosomes.

Nonrandom assembly of chromatin during hydroxyurea inhibition of DNA synthesis

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