Methylation of histone h3 at lysine 9 targets programmed DNA elimination in tetrahymena

Abstract

Histone H3 lysine 9 methylation [Me(Lys9)H3] is an epigenetic mark for heterochromatin-dependent gene silencing, mediated by direct binding to chromodomain-containing proteins such as Heterochromatin Protein 1. In the ciliate Tetrahymena, two chromodomain proteins, Pdd1p and Pdd3p, are involved in the massive programmed DNA elimination that accompanies macronuclear development. We report that both proteins bind H3(Lys9)Me in vitro. In vivo, H3(Lys9)Me is confined to the time period and location where DNA elimination occurs, and associates with eliminated sequences. Loss of parental Pdd1p expression drastically reduces H3(Lys9)Me. Finally, tethering Pdd1p is sufficient to promote DNA excision. These results extend the range of H3(Lys9)Me involvement in chromatin activities outside transcriptional regulation and also strengthen the link between heterochromatin formation and programmed DNA elimination.