Neurospora Importin α Is Required for Normal Heterochromatic Formation and DNA Methylation

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The epigenetic information contained in chromatin is essential for development of higher organisms, and if misregulated, can lead to the unregulated growth associated with human cancers. Chromatin is typically classified into two basic types: gene-rich 'euchromatin', and gene-poor heterochromatin, which is also rich in repeated DNA and 'repressive chromatin marks'. As in humans and eukaryotes generally, heterochromatin in Neurospora crassa is decorated with DNA methylation and histone H3 lysine 9 (H3K9) methylation, but unlike the case in mammals, loss of these epigenetic marks does not compromise viability. In Neurospora, the DCDC, a five-member Cul4-based protein complex, trimethylates H3K9. Little information is available on the regulation of DCDC or similar complexes in other organisms. Using forward genetics, we identified a novel role for Importin α (NUP-6) for the function of DCDC. Although NUP-6 typically functions in nucleocytoplasmic transport, the dim-3 strain, which contains an altered nup-6 gene that reduces DNA methylation and H3K9me3, shows normal nuclear transport of the heterochromatin machinery and a canonical transport substrate. Two DCDC members are mislocalized from heterochromatin in the dim-3 mutant, signifying that NUP-6 may be important for targeting key proteins to incipient heterochromatic DNA. The euchromatic complex SAGA has increased euchromatin localization in dim-3, suggesting that NUP-6 may localize multiple chromatin complexes to sub-nuclear genomic targets.

Vyšlo v časopise: Neurospora Importin α Is Required for Normal Heterochromatic Formation and DNA Methylation. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005083
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005083

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