Chromatin Motion Is Constrained by Association with Nuclear Compartments in Human Cells

BACKGROUND In comparison with many nuclear proteins, the movement of chromatin in nuclei appears to be generally constrained. These restrictions on motion are proposed to reflect the attachment of chromatin to immobile nuclear substructures. RESULTS To gain insight into the regulation of chromosome dynamics by nuclear architecture, we have followed the movements of different sites in the human genome in living cells. Here, we show that loci at nucleoli or the nuclear periphery are significantly less mobile than other, more nucleoplasmic loci. Disruption of nucleoli increases the mobility of nucleolar-associated loci. CONCLUSIONS This is the first report of distinct nuclear substructures constraining the movements of chromatin. These constraints reflect the physical attachment of chromatin to nuclear compartments or steric impairment caused by local ultrastructure. Our data suggest a role for the nucleolus and nuclear periphery in maintaining the three-dimensional organization of chromatin in the human nucleus.

[1]  S. Gasser,et al.  The Positioning and Dynamics of Origins of Replication in the Budding Yeast Nucleus , 2001, The Journal of cell biology.

[2]  John W. Sedat,et al.  Multiple regimes of constrained chromosome motion are regulated in the interphase Drosophila nucleus , 2001, Current Biology.

[3]  G. Church,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[4]  Peter Teague,et al.  Differences in the Localization and Morphology of Chromosomes in the Human Nucleus , 1999, The Journal of cell biology.

[5]  Daniel Axelrod,et al.  Chromatin Dynamics in Interphase Nuclei and Its Implications for Nuclear Structure , 1997, The Journal of cell biology.

[6]  Andrew S. Belmont,et al.  Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator , 2001, Nature Cell Biology.

[7]  A S Belmont,et al.  In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition , 1996, The Journal of cell biology.

[8]  Juliet A. Ellis,et al.  The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. , 2001, Human molecular genetics.

[9]  S. Gasser,et al.  Chromosome Dynamics in the Yeast Interphase Nucleus , 2001, Science.

[10]  D C Ward,et al.  Inhibition of RNA polymerase II transcription causes chromatin decondensation, loss of nucleolar structure, and dispersion of chromosomal domains. , 1996, Experimental cell research.

[11]  W. Bickmore,et al.  Chromosome bands--flavours to savour. , 1993, BioEssays : news and reviews in molecular, cellular and developmental biology.

[12]  Suraiya Rasheed,et al.  Characterization of a newly derived human sarcoma cell line (HT‐1080) , 1974, Cancer.

[13]  T. Misteli,et al.  High mobility of proteins in the mammalian cell nucleus , 2000, Nature.

[14]  R. Sternglanz,et al.  Perinuclear localization of chromatin facilitates transcriptional silencing , 1998, Nature.

[15]  Gail Sudlow,et al.  Interphase Cell Cycle Dynamics of a Late-Replicating, Heterochromatic Homogeneously Staining Region: Precise Choreography of Condensation/Decondensation and Nuclear Positioning , 1998, The Journal of cell biology.

[16]  B. Humbel,et al.  A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. , 1992, Journal of cell science.

[17]  Vieira Jeffrey,et al.  New pUC-derived cloning vectors with different selectable markers and DNA replication origins. , 1991 .

[18]  H. Berg Random Walks in Biology , 2018 .

[19]  C. Brun,et al.  Mapping of replication initiation sites in human ribosomal DNA by nascent-strand abundance analysis , 1995, Molecular and cellular biology.

[20]  W. Brown,et al.  Targeted breakage of a human chromosome mediated by cloned human telomeric DNA , 1992, Nature Genetics.

[21]  C. Fouet,et al.  Chromosomal constitution of nucleolus-associated chromatin in man , 1976, Human Genetics.

[22]  A S Belmont,et al.  Visualizing chromosome dynamics with GFP. , 2001, Trends in cell biology.

[23]  W. Bickmore,et al.  Genes and genomes: chromosome bands – flavours to savour , 1993 .

[24]  W. Bickmore,et al.  Putting the genome on the map. , 1998, Trends in genetics : TIG.

[25]  Thomas Cremer,et al.  Cell nucleus: Chromosome dynamics in nuclei of living cells , 1998, Current Biology.

[26]  D. Spector,et al.  Visualization of gene activity in living cells , 2000, Nature Cell Biology.

[27]  T. Cremer,et al.  Chromosome territories, nuclear architecture and gene regulation in mammalian cells , 2001, Nature Reviews Genetics.

[28]  Jean-Christophe Olivo-Marin,et al.  Nuclear pore complexes in the organization of silent telomeric chromatin , 2000, Nature.

[29]  A. Murray,et al.  Interphase chromosomes undergo constrained diffusional motion in living cells , 1997, Current Biology.

[30]  S. Henikoff,et al.  Genetic modification of heterochromatic association and nuclear organization in Drosophila , 1996, Nature.