Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation

Gideon Grafi, Hagit Ben-Meir, Yigal Avivi, Maya Moshe, Yardena Dahan, Assaf Zemach

    Research output: Contribution to journalArticlepeer-review

    82 Scopus citations

    Abstract

    Cellular dedifferentiation underlies topical issues in biology such as regeneration and nuclear cloning and has common features in plants and animals. In plants, this process characterizes the transition of differentiated leaf cells to protoplasts (plant cells devoid of cell walls) and is accompanied by global chromatin reorganization associated with reprogramming of gene expression. A screen for mutants defective in proliferation and callus formation identified kyp-2-a mutant in the KRYPTONITE (KYP)/SUVH4 gene encoding a histone H3 lysine 9 (H3K9) methyltransferase. Analysis of telomere length revealed stochastic telomerase-independent lengthening of telomeres in wild type but not in kyp-2 protoplasts. In kyp-2 mutant, telomeric repeats were no longer associated with dimethylated H3K9. The Arabidopsis telomerase reverse transcriptase (tert) mutant displayed accelerated proliferation despite its short telomeres, though it also showed accelerated cell death. Microarray analysis uncovered several components of the ubiquitin proteolytic system, which are downregulated in kyp-2 compared to wild-type protoplasts. Thus, our results suggest that histone methylation activity is required for the establishment/maintenance of the dedifferentiated state and/or reentry into the cell cycle, at least partly, through activation of genes whose products are involved in the ubiquitin proteolytic pathway. In addition, our results illuminate the complexity of cellular dedifferentiation, particularly the occurrence of DNA recombination that can lead to genome instability.

    Original languageEnglish
    Pages (from-to)838-846
    Number of pages9
    JournalDevelopmental Biology
    Volume306
    Issue number2
    DOIs
    StatePublished - 15 Jun 2007

    Keywords

    • Alternative lengthening of telomeres (ALT)
    • Arabidopsis
    • Callus
    • Chromatin
    • Dedifferentiation
    • Histone methylation
    • Pluripotency
    • Proliferation
    • Protoplasts
    • Telomeres

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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