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Chromatin assembly by DNA-translocating motors

Nature Reviews Molecular Cell Biology volume 4, pages 613–620 (2003)Cite this article

Key Points

  • Chromatin assembly in vivo occurs during DNA replication in cycling cells and in a replication-independent fashion throughout the cell cycle.

  • Histone chaperones, such as CAF1, RCAF/ASF1, NAP1 and HIR proteins, bind to histones and participate in their deposition onto DNA.

  • ATP-dependent factors, such as ACF and RSF, use the energy of ATP hydrolysis to assemble periodic arrays of nucleosomes.

  • ACF seems to function as a DNA-translocating enzyme during chromatin assembly.

  • In the iterative-annealing model for chromatin assembly, non-nucleosomal histone–DNA complexes are resolved into nucleosomes through the iterative disruption and re-establishment of histone–DNA contacts by an ATP-driven DNA-translocating enzyme.

  • In the directed-deposition model for chromatin assembly, a DNA-translocating motor functions in conjunction with the histone–chaperone complex to mediate the processive formation of nucleosome arrays.

Abstract

Chromatin assembly is required for the duplication of eukaryotic chromosomes and functions at the interface between cell-cycle progression and gene expression. The central machinery that mediates chromatin assembly consists of histone chaperones, which deliver histones to the DNA, and ATP-utilizing motor proteins, which are DNA-translocating factors that act in conjunction with the histone chaperones to mediate the deposition of histones into periodic nucleosome arrays. Here, we describe these factors and propose possible mechanisms by which DNA-translocating motors might catalyse chromatin assembly.

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Figure 1: A simple view of chromatin assembly.
Figure 2: Iterative-annealing model of chromatin assembly.
Figure 3: Nucleosome mobilization by a DNA-translocating enzyme.
Figure 4: Directed-deposition model of chromatin assembly.

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Acknowledgements

We thank D. Fyodorov, D. Smith and G. Gemmen for insightful discussions. We further thank D. Fyodorov, B. Santoso, J.-Y. Hsu, T. Juven-Gershon, T. Boulay and V. Alexiadis for critical reading of the manuscript. We apologize to our colleagues whose work could not be cited due to space limitations. K.A.H. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation. This work was supported by grants from the National Institutes of Health and the VolkswagenStiftung (to J.T.K.)

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  1. Section of Molecular Biology, University of California, 9500 Gilman Drive, La Jolla, San Diego, 92093-0347, California, USA

    Karl A. Haushalter & James T. Kadonaga

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  1. Karl A. Haushalter
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Correspondence to James T. Kadonaga.

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DATABASES

Flybase

Brahma

CHRAC14

CHRAC16

DF31

NAP1

ISWI

Saccharomyces Genome Database

Asf1

Hir1

Hir2

Kap114

Spt6

Swiss-Prot

ACF1

CAF1

HP1

N1/N2

NAP2

nucleophosmin/B23

nucleoplasmin

RAD53

hSNF2H

TFIID

Glossary

HIGH MOBILITY GROUP PROTEINS

(HMG proteins). Abundant, non-histone chromosomal proteins. There are three families of HMG proteins: HMGB (HMG1/2), HMGN (HMG14/17) and HMGA (HMG-I/-Y).

HETEROCHROMATIN

Chromatin that remains in a condensed state throughout the cell cycle; for example, centromeres and telomeres are heterochromatic regions. Few protein-coding genes are located in heterochromatin and most protein-coding genes are located in euchromatin, which decondenses during interphase.

PCNA

(Proliferating cell nuclear antigen). PCNA is a sliding-clamp protein that forms a doughnut-shaped structure around the DNA, and functions to increase the processivity of DNA polymerases.

KARYOPHERIN

Nuclear import receptor, also known as importin.

CHRAC

(Chromatin accessibility complex). CHRAC was originally identified as a factor that increases the accessibility of restriction enzymes to DNA that is packaged into chromatin.

NURF

(Nucleosome-remodelling factor). NURF was isolated on the basis of its ability to modify the chromatin structure at the hsp70 promoter in cooperation with transcription factors.

TRF2

(TATA-box-binding protein (TBP)-related factor 2). TRF2-containing complexes are involved in transcriptional regulation.

TOPOISOMERASE II

An abundant, ATP-dependent topoisomerase that functions by creating a double-stranded break in the DNA, passing another DNA molecule through this break, and then resealing the double-stranded break. The strand passage reaction relaxes supercoiled substrates and requires ATP.

NUCLEOSOME SLIDING

The translational movement of nucleosomal histones relative to the DNA. Because of the asymmetry of the histone–DNA contacts in the nucleosome, it is unlikely that the histones actually 'slide' along the DNA.

WAC MOTIF

A protein sequence motif that was initially found in WSTF (Williams syndrome transcription factor), ACF1 and cbp147. The WAC motif in ACF1 was found to be required for binding of ACF to DNA.

WAKZ MOTIF

A protein sequence motif that was initially found in WSTF (Williams syndrome transcription factor), ACF1, KIAA0314 and ZK783.4.

DDT DOMAIN

A protein sequence motif found in transcription and chromatin-modifying factors. The sub-region of ACF1 that interacts with ISWI contains a DDT domain.

PHD FINGER

A protein sequence motif that was termed plant homeodomain finger. The PHD finger is found in many proteins that function with chromatin.

BROMODOMAIN

A protein sequence motif that is present in many chromatin-modifying proteins. Bromodomains have been found to bind to acetylated lysine residues.

TRIPLEX DNA DISPLACEMENT ASSAY

A test for DNA translocation in which a short oligonucleotide that binds in the major groove of a pyrimidine-rich target sequence is displaced by motor proteins that translocate through the sequence.

CHAPERONIN

ATP-dependent protein complex that mediates protein folding.

NUCLEOSOME MOBILITY

The ability of nucleosomal histones to move along the DNA. Under physiological conditions, nucleosomes are essentially immobile, but some chromatin-remodelling factors are able to catalyse the movement of nucleosomes.

NUCLEOSOME REMODELLING

Also known as chromatin remodelling. Any detectable change in histone–DNA interactions in a nucleosome. Chromatin-remodelling factors alter the structure of nucleosomes in an ATP-dependent manner.

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Haushalter, K., Kadonaga, J. Chromatin assembly by DNA-translocating motors. Nat Rev Mol Cell Biol 4, 613–620 (2003). https://doi.org/10.1038/nrm1177

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