| Popis: |
Chemical modifications to histones and DNA are critical for the establishment of distinct chromatin states and the regulation of the underlying DNA sequence. Aberrant heterochromatin, often with hyper- or hypomethylated DNA, is associated with many human disease states, including cancers, but the mechanisms controlling heterochromatin establishment are not fully understood. We developed in vivo protein tethering in Neurospora crassa, a filamentous fungus harboring many aspects of heterochromatin found in higher eukaryotes, and used it to direct heterochromatin to normally active, euchromatic loci. Testing tethered heterochromatin factors in various mutant backgrounds revealed interrelationships among the classic hallmarks of heterochromatin: DNA methylation, histone deacetylation, and H3K9me3. We also found evidence of complex regulation of the DIM-2 DNA methyltransferase. |
