The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas

J. Armando Casas-Mollano, Byeong Ryool Jeong, Jianping Xu, Hideaki Moriyama, Heriberto Cerutti

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Changes in chromatin organization are emerging as key regulators in nearly every aspect of DNA-templated metabolism in eukaryotes. Histones undergo many, largely reversible, posttranslational modifications that affect chromatin structure. Some modifications, such as trimethylation of histone H3 on Lys 4 (H3K4me3), correlate with transcriptional activation, whereas others, such as methylation of histone H3 on Lys 27 (H3K27me), are associated with silent chromatin. Posttranslational histone modifications may also be involved in the inheritance of chromatin states. Histone phosphorylation has been implicated in a variety of cellular processes but, because of the dynamic nature of this modification, its potential role in long-term gene silencing has remained relatively unexplored. We report here that a Chlamydomonas reinhardtii mutant defective in a Ser/Thr protein kinase (MUT9p), which phosphorylates histones H3 and H2A, shows deficiencies in the heritable repression of transgenes and transposons. Moreover, based on chromatin immunoprecipitation analyses, phosphorylated H3T3 (H3T3ph) and monomethylated H3K4 (H3K4me1) are inversely correlated with di/trimethylated H3K4 and associate preferentially with silenced transcription units. Conversely, the loss of those marks in mutant strains correlates with the transcriptional reactivation of transgenes and transposons. Our results suggest that H3T3ph and H3K4me1 function as reinforcing epigenetic marks for the silencing of euchromatic loci in Chlamydomonas.

Original languageEnglish (US)
Pages (from-to)6486-6491
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number17
DOIs
StatePublished - Apr 29 2008

Keywords

  • Gene silencing
  • Histone phosphorylation

ASJC Scopus subject areas

  • General

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