Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation

Gerard L. Brien; Guillermo Gambero; David J. O'Connell; Emilia Jerman; Siobhán A. Turner; Chris M. Egan; Eiseart J. Dunne; Maike C. Jurgens; Kieran Wynne; Lianhua Piao; Amanda J. Lohan; Neil Ferguson; Xiaobing Shi; Krishna M. Sinha; Brendan J. Loftus; Gerard Cagney; Adrian P. Bracken

doi:10.1038/nsmb.2449

Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation

Gerard L. Brien
, Guillermo Gambero
, David J. O'Connell
, Emilia Jerman
, Siobhán A. Turner
, Chris M. Egan
, Eiseart J. Dunne
, Maike C. Jurgens
, Kieran Wynne
, Lianhua Piao
, Amanda J. Lohan
, Neil Ferguson
, Xiaobing Shi
, Krishna M. Sinha
, Brendan J. Loftus
, Gerard Cagney
, Adrian P. Bracken

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

Abstract

Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36 (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2 complex and NO66 to stem cell genes during differentiation, leading to PRC2-mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state.

Original language	English
Pages (from-to)	1273-1281
Number of pages	9
Journal	Nature Structural and Molecular Biology
Volume	19
Issue number	12
DOIs	https://doi.org/10.1038/nsmb.2449
Publication status	Published - Dec 2012
Externally published	Yes

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Brien, G. L., Gambero, G., O'Connell, D. J., Jerman, E., Turner, S. A., Egan, C. M., Dunne, E. J., Jurgens, M. C., Wynne, K., Piao, L., Lohan, A. J., Ferguson, N., Shi, X., Sinha, K. M., Loftus, B. J., Cagney, G., & Bracken, A. P. (2012). Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation. Nature Structural and Molecular Biology, 19(12), 1273-1281. https://doi.org/10.1038/nsmb.2449

@article{dd22e444eb8b4daaa6aa63a341852114,

title = "Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation",

abstract = "Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36 (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2 complex and NO66 to stem cell genes during differentiation, leading to PRC2-mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state.",

author = "Brien, \{Gerard L.\} and Guillermo Gambero and O'Connell, \{David J.\} and Emilia Jerman and Turner, \{Siobh{\'a}n A.\} and Egan, \{Chris M.\} and Dunne, \{Eiseart J.\} and Jurgens, \{Maike C.\} and Kieran Wynne and Lianhua Piao and Lohan, \{Amanda J.\} and Neil Ferguson and Xiaobing Shi and Sinha, \{Krishna M.\} and Loftus, \{Brendan J.\} and Gerard Cagney and Bracken, \{Adrian P.\}",

year = "2012",

month = dec,

doi = "10.1038/nsmb.2449",

language = "English",

volume = "19",

pages = "1273--1281",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Research",

number = "12",

}

Brien, GL, Gambero, G, O'Connell, DJ, Jerman, E, Turner, SA, Egan, CM, Dunne, EJ, Jurgens, MC, Wynne, K, Piao, L, Lohan, AJ, Ferguson, N, Shi, X, Sinha, KM, Loftus, BJ, Cagney, G & Bracken, AP 2012, 'Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation', Nature Structural and Molecular Biology, vol. 19, no. 12, pp. 1273-1281. https://doi.org/10.1038/nsmb.2449

TY - JOUR

T1 - Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation

AU - Brien, Gerard L.

AU - Gambero, Guillermo

AU - O'Connell, David J.

AU - Jerman, Emilia

AU - Turner, Siobhán A.

AU - Egan, Chris M.

AU - Dunne, Eiseart J.

AU - Jurgens, Maike C.

AU - Wynne, Kieran

AU - Piao, Lianhua

AU - Lohan, Amanda J.

AU - Ferguson, Neil

AU - Shi, Xiaobing

AU - Sinha, Krishna M.

AU - Loftus, Brendan J.

AU - Cagney, Gerard

AU - Bracken, Adrian P.

PY - 2012/12

Y1 - 2012/12

N2 - Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36 (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2 complex and NO66 to stem cell genes during differentiation, leading to PRC2-mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state.

AB - Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb repressive complex 2 (PRC2) component PHF19 binds trimethylated histone H3 Lys36 (H3K36me3), a mark of active chromatin, via its Tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and it is required to recruit the PRC2 complex and NO66 to stem cell genes during differentiation, leading to PRC2-mediated trimethylation of histone H3 Lys27 (H3K27), loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during mouse embryonic stem cell differentiation to transiently bind the H3K36me3 mark via its Tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state.

UR - https://www.scopus.com/pages/publications/84870825642

U2 - 10.1038/nsmb.2449

DO - 10.1038/nsmb.2449

M3 - Article

C2 - 23160351

AN - SCOPUS:84870825642

SN - 1545-9993

VL - 19

SP - 1273

EP - 1281

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 12

ER -

Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation

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