Attachment to the nuclear matrix mediates specific alterations in chromatin structure

Pemov, Alexander; Bavykin, Sergei G.; Hamlin, Joyce L.

doi:10.1073/pnas.95.25.14757

Cited by 56 publications

(43 citation statements)

References 69 publications

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“…We have not compared lamin B localization to early S-phase replication foci in primary cells, although the reported localization pattern for this protein in other cell types does not coincide with the nucleolus. Finally, a number of reports have suggested that sites of DNA replication are associated with genomic matrix attachment regions (Dingman 1974;Pardoll et al 1980;Amati and Gasser 1990;Jackson and Pombo 1998;Pemov et al 1998). Asynchronous populations of cells at low density were pulsed with BrdU and analyzed for replication patterns.…”

Section: Constitution Of the Perinucleolar Replication Focimentioning

confidence: 99%

Nuclear organization of DNA replication in primary mammalian cells

Kennedy¹,

Barbie²,

Classon³

et al. 2000

Genes Dev.

270

240

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Using methods that conserve nuclear architecture, we have reanalyzed the spatial organization of the initiation of mammalian DNA synthesis. Contrary to the commonly held view that replication begins at hundreds of dispersed nuclear sites, primary fibroblasts initiate synthesis in a limited number of foci that contain replication proteins, surround the nucleolus, and overlap with previously identified internal lamin A/C structures. These foci are established in early G 1 -phase and also contain members of the retinoblastoma protein family. Later, in S-phase, DNA replication sites distribute to regions located throughout the nucleus. As this progression occurs, association with the lamin structure and pRB family members is lost. A similar temporal progression is found in all the primary cells we have examined but not in most established cell lines, indicating that the immortalization process modifies spatial control of DNA replication. These findings indicate that in normal mammalian cells, the onset of DNA synthesis is coordinately regulated at a small number of previously unrecognized perinucleolar sites that are selected in early G 1 -phase.

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Section: Constitution Of the Perinucleolar Replication Focimentioning

confidence: 99%

Nuclear organization of DNA replication in primary mammalian cells

Kennedy¹,

Barbie²,

Classon³

et al. 2000

Genes Dev.

270

240

View full text Add to dashboard Cite

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“…A subset of MARs is believed to mediate the organization of chromatin into a higher order structure consisting of multiple topologically constrained loops attached at their bases to the matrix (2). A role for MARs in DNA replication has been proposed because many MARs contain origins of replication, and newly replicated DNA is anchored to the nuclear matrix (3). The mapping of MARs to 5Ј-regulatory regions of certain genes, to actively transcribing genes, and to sites for binding activator, repressor, and demethylation proteins suggests that MARs also play a role in gene regulation (1,4).…”

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confidence: 99%

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

Donev

Horton

Beck

et al. 2003

Journal of Biological Chemistry

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Sequences containing the matrix recognition signature were identified adjacent to the LMP/TAP gene cluster in the human and mouse major histocompatibility complex class II region. These sequences were shown to function as nuclear matrix attachment regions (MARs). Three of the five human MARs and the single mouse MAR recruit heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) in vivo during transcriptional up-regulation of the major histocompatibility complex class II genes. The timing of this recruitment correlates with a rise in mature TAP1 mRNA. Two of the human MARs bind hnRNP-A1 in vitro directly within a 35-bp sequence that shows over 90% similarity to certain Alu repeat sequences. This study shows that MARs recruit and bind hnRNP-A1 upon transcriptional up-regulation.

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“…MARs are operationally defined in MAR assays by their ability to associate to a nuclear matrix or scaffold (17) and have been implicated in the regulation of chromatin structure and gene expression. They are frequently associated with enhancers (4, 10, 11) and promote chromatin accessibility and histone acetylation (7,9,15,20,26). MARs may also sometimes act as boundaries, preventing the spreading of potential repressive effects from the adjacent chromatin (25).…”

mentioning

confidence: 99%

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

Weber

Hagège

Murrell

et al. 2003

Molecular and Cellular Biology

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Genomic imprinting at the Igf2/H19 locus originates from allele-specific DNA methylation, which modifies the affinity of some proteins for their target sequences. Here, we show that AT-rich DNA sequences located in the vicinity of previously characterized differentially methylated regions (DMRs) of the imprinted Igf2 gene are conserved between mouse and human. These sequences have all the characteristics of matrix attachment regions (MARs), which are known as versatile regulatory elements involved in chromatin structure and gene expression. Combining allele-specific nuclear matrix binding assays and real-time PCR quantification, we show that retention of two of these Igf2 MARs (MAR0 and MAR2) in the nuclear matrix fraction depends on the tissue and is specific to the paternal allele. Furthermore, on this allele, the Igf2 MAR2 is functionally linked to the neighboring DMR2 while, on the maternal allele, it is controlled by the imprinting-control region. Our work clearly demonstrates that genomic imprinting controls matrix attachment regions in the Igf2 gene.On the distal part of mouse chromosome 7, the Igf2 and H19 genes are separated by 72 kbp. At this locus, imprinting originates from paternal germ line-specific methylation that impairs the binding of a protein factor (CTCF) to the intergenic imprinting-control region (ICR). On the maternal allele, binding of CTCF results in activation of an insulator, which prevents Igf2 expression by blocking promoter access to a set of enhancers located downstream of H19 (2, 14). Thus, Igf2 gene expression is restricted to the paternal allele, whereas H19 is maternally expressed. However, Igf2 imprinting also involves additional differentially methylated regions (DMR0, DMR1, and DMR2) that control regional epigenetic modifications in a hierarchical and tissue-specific fashion (19). DMR1, located upstream of the fetal Igf2 promoters, is preferentially methylated on the paternal allele and acts as a methylation-sensitive silencer in several mesodermal tissues (5). DMR2 maps to exons 5 to 6 and augments transcription on the methylated paternal allele (24). Finally, DMR0 is maternally methylated in the placenta and overlaps the placenta-specific P0 promoter (23). All these DMRs display tissue-specific methylation patterns, and we have recently proposed that their methylation profiles are regionally coordinated through long-range chromatin interactions (19).Here, we identify intragenic AT-rich DNA sequences in the Igf2 gene that are contiguous to previously identified DMRs. These sequences have all the characteristics of matrix attachment regions (MARs) and are conserved in humans. MARs are operationally defined in MAR assays by their ability to associate to a nuclear matrix or scaffold (17) and have been implicated in the regulation of chromatin structure and gene expression. They are frequently associated with enhancers (4, 10, 11) and promote chromatin accessibility and histone acetylation (7,9,15,20,26). MARs may also sometimes act as boundaries, preventing the spreading of p...

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Attachment to the nuclear matrix mediates specific alterations in chromatin structure

Cited by 56 publications

References 69 publications

Nuclear organization of DNA replication in primary mammalian cells

Nuclear organization of DNA replication in primary mammalian cells

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

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