TY - JOUR
T1 - Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication
AU - Jacob, Yannick
AU - Bergamin, Elisa
AU - Donoghue, Mark T.A.
AU - Mongeon, Vanessa
AU - LeBlanc, Chantal
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.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1248357
DO - 10.1126/science.1248357
M3 - Article
C2 - 24626927
AN - SCOPUS:84896033884
VL - 343
SP - 1249
EP - 1253
JO - Science
JF - Science
SN - 0036-8075
IS - 6176
ER -