Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication

Yannick Jacob; Elisa Bergamin; Mark T.A. Donoghue; Vanessa Mongeon; Chantal LeBlanc; Philipp Voigt; Charles J. Underwood; Joseph S. Brunzelle; Scott D. Michaels; Danny Reinberg; Jean François Couture; Robert A. Martienssen

doi:10.1126/science.1248357

Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication

Yannick Jacob, Elisa Bergamin, Mark T.A. Donoghue, Vanessa Mongeon, Chantal LeBlanc, Philipp Voigt, Charles J. Underwood, Joseph S. Brunzelle, Scott D. Michaels, Danny Reinberg, Jean François Couture^*, Robert A. Martienssen

^*Corresponding author for this work

NSRC - Northwestern Synchrotron Research Center - LS CAT

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

88 Scopus citations

Abstract

Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically "reads" alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.

Original language	English (US)
Pages (from-to)	1249-1253
Number of pages	5
Journal	Science
Volume	343
Issue number	6176
DOIs	https://doi.org/10.1126/science.1248357
State	Published - 2014

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Jacob, Yannick ; Bergamin, Elisa ; Donoghue, Mark T.A. ; Mongeon, Vanessa ; LeBlanc, Chantal ; Voigt, Philipp ; Underwood, Charles J. ; Brunzelle, Joseph S. ; Michaels, Scott D. ; Reinberg, Danny ; Couture, Jean François ; Martienssen, Robert A. / Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. In: Science. 2014 ; Vol. 343, No. 6176. pp. 1249-1253.

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title = "Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication",

abstract = "Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically {"}reads{"} alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.",

author = "Yannick Jacob and Elisa Bergamin and Donoghue, {Mark T.A.} and Vanessa Mongeon and Chantal LeBlanc and Philipp Voigt and Underwood, {Charles J.} and Brunzelle, {Joseph S.} and Michaels, {Scott D.} and Danny Reinberg and Couture, {Jean Fran{\c c}ois} and Martienssen, {Robert A.}",

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Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. / Jacob, Yannick; Bergamin, Elisa; Donoghue, Mark T.A.; Mongeon, Vanessa; LeBlanc, Chantal; Voigt, Philipp; Underwood, Charles J.; Brunzelle, Joseph S.; Michaels, Scott D.; Reinberg, Danny; Couture, Jean François; Martienssen, Robert A.

In: Science, Vol. 343, No. 6176, 2014, p. 1249-1253.

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

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AU - Voigt, Philipp

AU - Underwood, Charles J.

AU - Brunzelle, Joseph S.

AU - Michaels, Scott D.

AU - Reinberg, Danny

AU - Couture, Jean François

AU - Martienssen, Robert A.

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