An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

Magnus D Lynch; Andrew Smith; Marco De Gobbi; Maria Flenley; Jim R Hughes; Douglas Vernimmen; Helena Ayyub; Jacqueline A Sharpe; Jacqueline A Sloane-Stanley; Linda Sutherland; Stephen Meek; Tom Burdon; Richard J Gibbons; David Garrick; Douglas R Higgs

doi:10.1038/emboj.2011.399

An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

Magnus D Lynch, Andrew Smith, Marco De Gobbi, Maria Flenley, Jim R Hughes, Douglas Vernimmen, Helena Ayyub, Jacqueline A Sharpe, Jacqueline A Sloane-Stanley, Linda Sutherland, Stephen Meek, Tom Burdon, Richard J Gibbons, David Garrick, Douglas R Higgs

Research output: Contribution to journal › Article › peer-review

Abstract

The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells.

Original language	English
Pages (from-to)	317-329
Number of pages	13
Journal	EMBO Journal
Volume	31
Issue number	2
Early online date	4 Nov 2011
DOIs	https://doi.org/10.1038/emboj.2011.399
Publication status	Published - Jan 2012

Keywords / Materials (for Non-textual outputs)

chromatin bivalency
CpG islands
Polycomb
stem cells
transcriptional regulation

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10.1038/emboj.2011.399

17 Lynch 2011
Copyright © 2012, European Molecular Biology Organization
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http://www.nature.com/emboj/journal/v31/n2/full/emboj2011399a.html

Cite this

Lynch, M. D., Smith, A., De Gobbi, M., Flenley, M., Hughes, J. R., Vernimmen, D., Ayyub, H., Sharpe, J. A., Sloane-Stanley, J. A., Sutherland, L., Meek, S., Burdon, T., Gibbons, R. J., Garrick, D., & Higgs, D. R. (2012). An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. EMBO Journal, 31(2), 317-329. https://doi.org/10.1038/emboj.2011.399

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abstract = "The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells.",

keywords = "chromatin bivalency , CpG islands , Polycomb, stem cells, transcriptional regulation",

author = "Lynch, {Magnus D} and Andrew Smith and {De Gobbi}, Marco and Maria Flenley and Hughes, {Jim R} and Douglas Vernimmen and Helena Ayyub and Sharpe, {Jacqueline A} and Sloane-Stanley, {Jacqueline A} and Linda Sutherland and Stephen Meek and Tom Burdon and Gibbons, {Richard J} and David Garrick and Higgs, {Douglas R}",

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Lynch, MD, Smith, A, De Gobbi, M, Flenley, M, Hughes, JR, Vernimmen, D, Ayyub, H, Sharpe, JA, Sloane-Stanley, JA, Sutherland, L, Meek, S , Burdon, T, Gibbons, RJ, Garrick, D & Higgs, DR 2012, 'An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment', EMBO Journal, vol. 31, no. 2, pp. 317-329. https://doi.org/10.1038/emboj.2011.399

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AU - Burdon, Tom

AU - Gibbons, Richard J

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AB - The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells.

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An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

Abstract

Keywords / Materials (for Non-textual outputs)

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Control of development and reproductive traits

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An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Other files and links

Fingerprint

Projects

Control of development and reproductive traits

EURATRANS

Cite this