Progressive methylation of ageing histones by Dot1 functions as a timer

Dot1 对衰老组蛋白进行甲基化,起到计时器的作用

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作者:Dirk De Vos, Floor Frederiks, Marit Terweij, Tibor van Welsem, Kitty F Verzijlbergen, Ekaterina Iachina, Erik L de Graaf, A F Maarten Altelaar, Gideon Oudgenoeg, Albert J R Heck, Jeroen Krijgsveld, Barbara M Bakker, Fred van Leeuwen

Abstract

Post-translational modifications of histone proteins have a crucial role in regulating gene expression. If efficiently re-established after chromosome duplication, histone modifications could help propagate gene expression patterns in dividing cells by epigenetic mechanisms. We used an integrated approach to investigate the dynamics of the conserved methylation of histone H3 Lys 79 (H3K79) by Dot1. Our results show that methylation of H3K79 progressively changes after histone deposition, which is incompatible with a rapid copy mechanism. Instead, methylation accumulates on ageing histones, providing the cell with a timer mechanism to directly couple cell-cycle length to changes in chromatin modification on the nucleosome core.

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