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Mechanisms of transcriptional memory

Nature Reviews Molecular Cell Biology volume 2, pages 409–421 (2001)Cite this article

Key Points

  • PcG and trxG genes comprise a maintenance system for gene expression.

  • PcG repression is targeted to silent genes, suggesting that these proteins differentiate between active and inactive states; PcG and trxG might differentially recognize chromatin features of active versus inactive genes.

  • PcG repression might occur through effects on chromatin structure.

  • Models for how PcG proteins repress gene expression suggest that PcG proteins are a structural component of repressed chromatin, or alternatively, have chromatin-organizing properties.

  • PcG proteins form large complexes, the biochemical activities of which are largely unknown but might include histone modification.

  • The trxG maintains active gene expression, probably also at the level of chromatin structure.

  • Some trxG genes encode components of chromatin-remodelling complexes.

  • Targeting of PcG and trxG complexes might occur through sequence-specific DNA-binding proteins that are implicated in both PcG and trxG function.

  • It is not known how PcG and trxG proteins maintain expression states through cell division, but stable marks on chromatin probably have a role.

Abstract

How can the same gene remember that it is 'off' in one cell lineage and 'on' in another? Studies of how homeotic genes are regulated in Drosophila melanogaster have uncovered a transcriptional maintenance system, encoded by the Polycomb and trithorax group genes, that preserves expression patterns across development. Here we try to formulate a broad framework for the types of molecular mechanism used by the Polycomb and trithorax proteins.

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Figure 1: Repression of transcription by PcG complexes.
Figure 2: Models for action of PcG proteins over long distances.
Figure 4: Three models for how PcG proteins might maintain contact with a gene through replication and/or mitosis.
Figure 3: Hypothetical model for recruitment of PcG or trxG proteins to the same gene.

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Acknowledgements

We apologize to our colleagues whose papers we were unable to reference owing to space limitations. We thank Ian King, Niveen Malek and anonymous reviewers for helpful comments. Work in the laboratory of R.E.K. is supported by grants from the NIH, and N.J.F is supported by a fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation.

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Authors and Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Nicole J. Francis & Robert E. Kingston

  2. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Nicole J. Francis & Robert E. Kingston

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  1. Nicole J. Francis
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DATABASE LINKS

Pc

Psc

Sir2

Su(var)3-9

Esc

E(z)

Mi-2

Rpd3

p55

Scm

SUV39H1

HP1

Brm

Mor

Osa

Kohtalo

Kismet

Trx

Ash1

Ash2

Snr1

Swi1

BAF250

E(Pc)

Zeste

Crm

Su(z)2

Pho

YY1

EED

RYBP

RING1

E2F6

BMI1

ENCYCLOPEDIA OF LIFE SCIENCES

Gene silencing in development (Drosophila)

Glossary

EPIGENETIC

Effects on gene expression or function that are heritable through cell division.

SEGMENTATION GENES

Transcriptional regulators that establish initial patterns of homeotic gene expression.

HETEROCHROMATIN

Late replicating, gene sparse, condensed chromatin regions that are rich in repeated sequence.

POLYTENE CHROMOSOMES

The chromosomes found in Drosophila melanogaster salivary gland cells, which are replicated many times in the absence of strand separation or cell division. Often used in histological studies as the large number of DNA copies allow immunolocalization of DNA/chromatin-binding proteins and crude mapping to chromosome regions.

HISTONE METHYLTRANSFERASE

Enzyme that methylates histones; the only described histone methyltransferase is Su(var)3-9 and its mammalian homologues, which methylate histone H3 on lysine 9.

NURD

(Nucleosome remodelling and histone deacetylation). Complex containing both chromatin remodelling and histone deacetylation activities.

SAGA

(Spt–Ada–Gcn5-acetyltransferase). Histone acetylase and adapter complex identified in yeast that is implicated in transcriptional activation.

SWI/SNF

Chromatin-remodelling complex identified genetically in yeast as a group of genes required for mating type switching and growth on alternative sugar sources (sucrose non-fermenting mutants).

NURF

(Nucleosome remodelling factor). Chromatin remodelling complex isolated from Drosophila melanogaster embryos.

CAF1

(Chromatin assembly factor 1). Histone-binding protein that can act as a histone chaperone and is linked to chromatin assembly.

SET DOMAIN

(Su(var)3-9, Enhancer of Zeste, Trithorax). Sequence motif found in several chromatin-associated proteins, including members of both the trxG and PcG.

CHROMODOMAIN

Motif found in many chromatin-associated proteins, including members of both the PcG and trxG.

DNASE I-HYPERSENSITIVE SITE

Region of chromatin (usually less than a few hundred base pairs) that is ∼100 times more sensitive to digestion by DNaseI than bulk chromatin; can correspond to nucleosome-free regions. Many regulatory elements, including enhancers, promoters and insulators, map to DNAse I-hypersensitive sites.

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Francis, N., Kingston, R. Mechanisms of transcriptional memory. Nat Rev Mol Cell Biol 2, 409–421 (2001). https://doi.org/10.1038/35073039

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