Chromatin structure and dynamics: Functional implications

doi:10.1016/S0300-9084(01)01347-5

Biochimie

Volume 83, Issues 11–12, November–December 2001, Pages 1029-1039

https://doi.org/10.1016/S0300-9084(01)01347-5 Get rights and content

Abstract

In eucaryotes, DNA packaging into nucleosomes and its organization in a chromatin fiber generate constraints for all processes involving DNA, such as DNA-replication, -repair, -recombination, and -transcription. Transient changes in chromatin structure allow overcoming these constraints with different requirements in regions where processes described above are initiated. Mechanisms involved in chromatin dynamics are complex. Multiprotein complexes which can contain histone-acetyltransferase, -deacetylase, -methyltransferase or -kinase activities are targeted by regulatory factors to precise regions of the genome. These enzymes have been shown to modify histone-tails within specific nucleosomes. Post-translational modifications of histone-tails constitute a code that is thought to contribute to the nucleosome or to the chromatin fiber remodeling, either directly, or through the recruitment of other proteins. Other multiprotein complexes, such as ATP-dependent remodeling complexes, play an essential role in chromatin fiber dynamics allowing nucleosome sliding and redistribution on the DNA. We will focus here on the chromatin structure and its consequences for DNA damaging, replication, repair, and transcription and we will discuss the mechanisms of chromatin remodeling.

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.

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Chromatin structure and dynamics: Functional implications

Abstract

Section snippets

Chromatin structure

Chromatin remodeling

Chromatin structure and replication

Chromatin structure and DNA accessibility to damaging agents

Conclusion

Acknowledgements

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J. Biol. Chem.

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Proc. Natl. Acad. Sci. USA

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Nature

Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro

Proc. Natl. Acad. Sci. USA

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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