Chromatin structure and dynamics: Functional implications
Section snippets
Chromatin structure
The basic chromatin structure unit is the nucleosome. The nucleosome is formed by a histone octamer core around which 146 bp of DNA is wrapped. Figure 1A depicts in details the structure of the nucleosome. Histones H3 and H4 form a dimer, two H3-H4 dimers associate into a (H3-H4)2 tetramer. DNA wraps around this tetramer, forming a tetrameric particle. Histones H2A and H2B heterodimerize and heterodimers associate on each side of the tetrameric particle to form a nucleosome 〚1〛, 〚2〛. The linker
Chromatin remodeling
DNA transcription, replication, repair and/or recombination require DNA accessibility to factors involved in the initiation of such processes. In addition, protein complexes, which size is large compared to a nucleosome, should be able to scan the DNA packaged in chromatin. This requires sequential changes into chromatin structure.
To achieve such chromatin structural changes, two major mechanisms have been proposed: 1) the post-translational modification of histones; and 2) the action of
Chromatin structure and replication
There is a complex interplay between chromatin and replication: chromatin organization affects replication and replication affects chromatin assembly. During cell division all DNA has to replicate, whatever the chromatin structure is. In this regard, replication differs from transcription since, in a cell, only part of the genome is transcribed and this has been correlated with the partition of the genes between euchromatin and heterochromatin. In contrast, for both transcription and
Chromatin structure and DNA accessibility to damaging agents
DNA damaging agents have been widely used to probe chromatin organization either in the living cells or in isolated nuclei. This approach allowed to show that chromatin organization influences DNA accessibility to such agents. Hydroxyl radical cleavage of DNA either naked, or assembled in vitro in a single positioned nucleosome is shown in figure 6A. Naked DNA is cut almost randomly while DNA assembled in a precisely positioned nucleosome displays a 10 bp periodical cut. Figure 6B shows the
Conclusion
Because of its tight packaging in chromatin, DNA accessibility to damaging agent and to the complex enzymatic machinery implicated in all processes involving DNA metabolism is impeded. Initiation of processes such as replication or DNA repair will require the rearrangement of the chromatin structure to gain access to the DNA . Chromatin remodeling machineries and either transcription, replication or DNA repair complexes are physically and functionally linked. Therefore, one should consider
Acknowledgements
We are grateful to M. Grigoriev and A. Hamiche for stimulating discussions and to M.J. Masse and L. Vandel for critically reading the manuscript.
References (55)
- et al.
Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes
Cell
(2000) - et al.
Nucleosome dynamics. II. High flexibility of nucleosome entering and exiting DNAs to positive crossing. An ethidium bromide fluorescence study of mononucleosomes on DNA minicircles
J. Mol. Biol.
(1999) - et al.
The Toxoplasma adhesive protein MIC2 is proteolytically processed at multiple sites by two parasite-derived proteases
J. Biol. Chem.
(2000) - et al.
Nucleosome linking number change controlled by acetylation of histones H3 and H4
J. Biol. Chem.
(1990) - et al.
ATP-dependent histone octamer sliding mediated by the chromatin remodeling complex NURF
Cell
(1999) - et al.
Nucleosome movement by CHRAC and ISWI without disruption or trans-displacement of the histone octamer
Cell
(1999) - et al.
Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter
Cell
(1999) - et al.
Disparate replication properties of integrated and extrachromosomal forms of bovine papilloma virus in ID13 cells
J. Mol. Biol.
(1995) - et al.
Characterization of the bovine papilloma virus plasmid maintenance sequences
Cell
(1984) Origins of DNA replication that function in eukaryotic cells
Curr. Opin. Cell Biol.
(1993)
Structure of replicating simian virus 40 minichromosomes. The replication fork, core histone segregation and terminal structures
J. Mol. Biol.
Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin
Cell
The ins and outs of nucleosome assembly
Curr. Opin. Genet. Dev.
Migration of a Holliday junction through a nucleosome directed by the E. coli RuvAB motor protein
Mol. Cell
Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis
Cell
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Curr. Biol.
The establishment of the long terminal repeat of the mouse mammary tumor virus into CV-1 cells allows a functional analysis of steroid receptors
Biochim. Biophys. Acta
Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites
Cell
A region immediately adjacent to the origin of replication of bovine papilloma virus type 1 interacts in vitro with the nuclear matrix
Biochem. Biophys. Res. Commun.
Interactions of the catabolite activator protein (CAP) at the galactose and lactose promoters of Escherichia coli probed by hydroxyl radical footprinting. The second CAP molecule which binds at gal and the one CAP at lac may act to stimulate transcription in the same way
J. Biol. Chem.
Topography of the histone octamer surface: repeating structural motifs utilized in the docking of nucleosomal DNA
Proc. Natl. Acad. Sci. USA
Crystal structure of the nucleosome core particle at 2.8 A resolution
Nature
Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro
Proc. Natl. Acad. Sci. USA
Crystal structure of a nucleosome core particle containing the variant histone H2A.Z
Nat. Struct. Biol.
DNA repair: spot (light)s on chromatin
Curr. Biol.
Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter
EMBO J.
Effects of different DNA polymerases in ligation-mediated PCR: enhanced genomic sequencing and in vivo footprinting
Proc. Natl. Acad. Sci. USA
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