The Trithorax group protein ASH1 requires a combination of BAH domain and AT hooks, but not the SET domain, for ... View Full Text


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Article Info

DATE

2021-07-31

AUTHORS

Philipp A. Steffen, Christina Altmutter, Eva Dworschak, Sini Junttila, Attila Gyenesei, Xinzhou Zhu, Tobias Kockmann, Leonie Ringrose

ABSTRACT

The Drosophila Trithorax group (TrxG) protein ASH1 remains associated with mitotic chromatin through mechanisms that are poorly understood. ASH1 dimethylates histone H3 at lysine 36 via its SET domain. Here, we identify domains of the TrxG protein ASH1 that are required for mitotic chromatin attachment in living Drosophila. Quantitative live imaging demonstrates that ASH1 requires AT hooks and the BAH domain but not the SET domain for full chromatin binding in metaphase, and that none of these domains are essential for interphase binding. Genetic experiments show that disruptions of the AT hooks and the BAH domain together, but not deletion of the SET domain alone, are lethal. Transcriptional profiling demonstrates that intact ASH1 AT hooks and the BAH domain are required to maintain expression levels of a specific set of genes, including several involved in cell identity and survival. This study identifies in vivo roles for specific ASH1 domains in mitotic binding, gene regulation, and survival that are distinct from its functions as a histone methyltransferase. More... »

PAGES

215-234

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  • Identifiers

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    DIMENSIONS

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    31 schema:description The Drosophila Trithorax group (TrxG) protein ASH1 remains associated with mitotic chromatin through mechanisms that are poorly understood. ASH1 dimethylates histone H3 at lysine 36 via its SET domain. Here, we identify domains of the TrxG protein ASH1 that are required for mitotic chromatin attachment in living Drosophila. Quantitative live imaging demonstrates that ASH1 requires AT hooks and the BAH domain but not the SET domain for full chromatin binding in metaphase, and that none of these domains are essential for interphase binding. Genetic experiments show that disruptions of the AT hooks and the BAH domain together, but not deletion of the SET domain alone, are lethal. Transcriptional profiling demonstrates that intact ASH1 AT hooks and the BAH domain are required to maintain expression levels of a specific set of genes, including several involved in cell identity and survival. This study identifies in vivo roles for specific ASH1 domains in mitotic binding, gene regulation, and survival that are distinct from its functions as a histone methyltransferase.
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    39 ASH1 AT hooks
    40 ASH1 domains
    41 AT-hook
    42 BAH
    43 BAH domain
    44 Drosophila
    45 Drosophila Trithorax group (TrxG) protein ASH1
    46 H3
    47 SET domain
    48 Trithorax group (TrxG) protein ASH1
    49 TrxG protein ASH1
    50 attachment
    51 binding
    52 cell identity
    53 chromatin
    54 chromatin attachment
    55 chromatin binding
    56 combination
    57 deletion
    58 disruption
    59 domain
    60 experiments
    61 expression levels
    62 full chromatin binding
    63 function
    64 gene regulation
    65 genes
    66 genetic experiments
    67 group (TrxG) protein ASH1
    68 histone H3
    69 histone methyltransferase
    70 hooks
    71 identity
    72 intact ASH1 AT hooks
    73 interphase binding
    74 levels
    75 lysine 36
    76 mechanism
    77 metaphase
    78 methyltransferase
    79 mitotic binding
    80 mitotic chromatin
    81 mitotic chromatin attachment
    82 mitotic chromatin binding
    83 profiling
    84 protein ASH1
    85 regulation
    86 role
    87 set
    88 specific ASH1 domains
    89 specific set
    90 study
    91 survival
    92 transcriptional profiling
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