Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes

Taemi Kawahara, T. Nicolai Siegel, Alexandra K. Ingram, Sam Alsford, George A. M. Cross, David Horn

    Research output: Contribution to journalArticle

    45 Citations (Scopus)

    Abstract

    Chromatin modification is important for virtually all aspects of DNA metabolism but little is known about the consequences of such modification in trypanosomatids, early branching protozoa of significant medical and veterinary importance. MYST-family histone acetyltransferases in other species function in transcription regulation, DNA replication, recombination and repair. Trypanosoma brucei HAT3 was recently shown to acetylate histone H4K4 and we now report characterization of all three T. brucei MYST acetyltransferases (HAT1-3). First, GFP-tagged HAT1-3 all localize to the trypanosome nucleus. While HAT3 is dispensable, both HAT1 and HAT2 are essential for growth. Strains with HAT1 knock-down display mitosis without nuclear DNA replication and also specific de-repression of a telomeric reporter gene, a rare example of transcription control in an organism with widespread and constitutive polycistronic transcription. Finally, we show that HAT2 is responsible for H4K10 acetylation. By analogy to the situation in Saccharomyces cerevisiae, we discuss low-level redundancy of acetyltransferase function in T. brucei and suggest that two MYST-family acetyltransferases are essential due to the absence of a Gcn5 homologue. The results are also consistent with the idea that HAT1 contributes to establishing boundaries between transcriptionally active and repressed telomeric domains in T. brucei.

    Original languageEnglish
    Pages (from-to)1054-1068
    Number of pages15
    JournalMolecular Microbiology
    Volume69
    Issue number4
    DOIs
    Publication statusPublished - Aug 2008

    Keywords

    • HAT COMPLEX
    • CELL-CYCLE PROGRESSION
    • DNA-REPAIR
    • PUTATIVE ACETYLTRANSFERASE
    • ZINC-FINGER
    • GENE-EXPRESSION
    • ACETYLTRANSFERASE COMPLEXES
    • GENOME ORGANIZATION
    • SACCHAROMYCES-CEREVISIAE
    • BRUCEI

    Cite this

    Kawahara, Taemi ; Siegel, T. Nicolai ; Ingram, Alexandra K. ; Alsford, Sam ; Cross, George A. M. ; Horn, David. / Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes. In: Molecular Microbiology. 2008 ; Vol. 69, No. 4. pp. 1054-1068.
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    Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes. / Kawahara, Taemi; Siegel, T. Nicolai; Ingram, Alexandra K.; Alsford, Sam; Cross, George A. M.; Horn, David.

    In: Molecular Microbiology, Vol. 69, No. 4, 08.2008, p. 1054-1068.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes

    AU - Kawahara, Taemi

    AU - Siegel, T. Nicolai

    AU - Ingram, Alexandra K.

    AU - Alsford, Sam

    AU - Cross, George A. M.

    AU - Horn, David

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    AB - Chromatin modification is important for virtually all aspects of DNA metabolism but little is known about the consequences of such modification in trypanosomatids, early branching protozoa of significant medical and veterinary importance. MYST-family histone acetyltransferases in other species function in transcription regulation, DNA replication, recombination and repair. Trypanosoma brucei HAT3 was recently shown to acetylate histone H4K4 and we now report characterization of all three T. brucei MYST acetyltransferases (HAT1-3). First, GFP-tagged HAT1-3 all localize to the trypanosome nucleus. While HAT3 is dispensable, both HAT1 and HAT2 are essential for growth. Strains with HAT1 knock-down display mitosis without nuclear DNA replication and also specific de-repression of a telomeric reporter gene, a rare example of transcription control in an organism with widespread and constitutive polycistronic transcription. Finally, we show that HAT2 is responsible for H4K10 acetylation. By analogy to the situation in Saccharomyces cerevisiae, we discuss low-level redundancy of acetyltransferase function in T. brucei and suggest that two MYST-family acetyltransferases are essential due to the absence of a Gcn5 homologue. The results are also consistent with the idea that HAT1 contributes to establishing boundaries between transcriptionally active and repressed telomeric domains in T. brucei.

    KW - HAT COMPLEX

    KW - CELL-CYCLE PROGRESSION

    KW - DNA-REPAIR

    KW - PUTATIVE ACETYLTRANSFERASE

    KW - ZINC-FINGER

    KW - GENE-EXPRESSION

    KW - ACETYLTRANSFERASE COMPLEXES

    KW - GENOME ORGANIZATION

    KW - SACCHAROMYCES-CEREVISIAE

    KW - BRUCEI

    U2 - 10.1111/j.1365-2958.2008.06346.x

    DO - 10.1111/j.1365-2958.2008.06346.x

    M3 - Article

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    VL - 69

    SP - 1054

    EP - 1068

    JO - Molecular Microbiology

    JF - Molecular Microbiology

    SN - 0950-382X

    IS - 4

    ER -