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The in vivo functions of ATP-dependent chromatin-remodelling factors

Key Points

  • The biochemical activities of ATP-dependent chromatin-remodelling factors have been well studied, but their in vivo functions are relatively unknown.

  • SWI/SNF-like complexes are generally implicated in transcriptional activation. However, there is a growing body of evidence that they also function in negative regulation of transcription.

  • The factors in the ISWI class are implicated mainly in repression of transcription. In Drosophila melanogaster, ISWI might also affect higher-order chromatin structure.

  • The in vivo functions of the CHD1 and INO80 classes are not well understood. Indirect evidence indicates that they are involved in gene regulation, but more data are needed.

  • The areas of research that require more attention in the future include identification of the direct targets of chromatin-remodelling factors, the molecular mechanisms of chromatin remodelling in vivo, the regulation of the chromatin-remodelling factors, and the regulation of chromatin higher-order structure by these remodelling factors.

Abstract

ATP-dependent chromatin-remodelling factors regulate the accessibility of DNA to nuclear factors that are involved in cellular processes that depend on protein–DNA interactions. They probably accomplish this by using the energy of ATP hydrolysis to change the positions of nucleosomes on the DNA, or to change the structure of DNA within the nucleosomes. Although their mechanisms of action have been extensively studied in vitro, many questions remain about their functions in vivo.

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Figure 1: Structure of four classes of ATPase in ATP-dependent chromatin-remodelling factors.
Figure 2: The in vivo roles of ATP-dependent chromatin-remodelling factors.

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DATABASES

Flybase

brm

Chd1

hunchback

tramtrack

LocusLink

β-globin

HP1

<i>Saccharomyces</i> Genome Database

Arp4

Arp5

Arp7

Arp8

Arp9

Chd1

DDM1

Gcn5

HO

INO1

Isw1

Isw2

PHO8

REC104

Rpd3

Rvb1

Rvb2

Sth1

SUC2

Ume6

Swiss-Prot

ACF1

BRCA1

BRG1

BRM

histone H4

Ikaros

Ini1

interferon-β

ISWI

LacZ

Mi-2

MyoD

NURF301

pRB

RuvB

Sin3

Swi2/Snf2

Swi5

FURTHER READING

Encylopedia of Life Science

Chromatin remodelling and histone modification in transcription regulation

Glossary

HISTONE DEACETYLASE

(HDAC). An enzyme that removes acetyl groups from histones. Many HDACs function as co-repressors.

HISTONE ACETYLTRANSFERASE

(HAT). An enzyme that adds acetyl groups to histones. Many HATs function as co-activators.

CHROMATIN IMMUNOPRECIPITATION

(ChIP). A technique that isolates sequences from soluble DNA–chromatin extracts (complexes of DNA and protein) using antibodies that recognize specific chromosomal proteins.

PERI-IMPLANTATION STAGE

The stage in mammalian development in which embryos are about to implant to the uterus.

DOSAGE COMPENSATION

The mechanism by which expression levels from sex chromosomes are adjusted. In mammalian systems, one copy of the X chromosome is silenced in the female. By contrast, in Drosophila, genes on the male X chromosome are expressed at twofold levels.

POLYTENE CHROMOSOMES

Chromosomes that are found in Drosophila salivary glands, which go through several cycles of DNA synthesis without cell division. As a result, the chromosomes become large enough to be seen under a microscope.

WAC DOMAIN

The domain in several ISWI-containing subunits from yeast to humans. The function of this domain is unknown at present.

HETEROCHROMATIN

Condensed regions of chromatin that are generally repressive for transcription.

DNA METHYLTRANSFERASE

An enzyme that methylates DNA. In mammalian cells, cytosine residues in CG sequences are methylated.

CHROMODOMAIN

A domain that is conserved in several chromatin proteins. The chromodomain of heterochromatin protein 1 interacts with histone H3 methylated at lysine 9.

INTERBANDS

On inspection of polytene chromosomes under light microscopes, dark and light bands are visible. The light bands are known as interbands, and are believed to be rich in actively transcribed genes.

PUFFS

Regions on polytene chromosomes that are decondensed due to highly active transcription.

DNA HELICASE

An enzyme that separates the two DNA strands in a double helix. This results in the formation of regions of single-stranded DNA.

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Tsukiyama, T. The in vivo functions of ATP-dependent chromatin-remodelling factors. Nat Rev Mol Cell Biol 3, 422–429 (2002). https://doi.org/10.1038/nrm828

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