DNA methylation, methylation of histone H3 at Lys9 (H3K9me3) and hypoacetylated histones are common molecular features of heterochromatin. Important details of their functions and inter-relationships remain unclear, however. In Neurospora crassa, H3K9me3 directs DNA methylation through a complex containing heterochromatin protein 1 (HP1) and the DNA methyltransferase DIM-2. We identified a distinct HP1 complex, HP1, CDP-2, HDA-1 and CHAP (HCHC), and found that it is responsible for silencing independently of DNA methylation. HCHC defects cause hyperacetylation of centromeric histones, greater accessibility of DIM-2 and hypermethylation of centromeric DNA. Loss of HCHC also causes mislocalization of the DIM-5 H3K9 methyltransferase at a subset of interstitial methylated regions, leading to selective DNA hypomethylation. We demonstrate that HP1 forms distinct DNA methylation and histone deacetylation complexes that work in parallel to assemble silent chromatin in N. crassa.
Bibliographical noteFunding Information:
We thank L.L. David and members of his proteomics facility at Oregon Health Sciences University for identifying DIM-2-associated proteins and T. Khalafallah for technical support in preliminary work. E.U.S. thanks S. Gasser and D. Schübeler (F. Miescher Institute) and G. Almouzni (Institut Curie) for hosting him during a sabbatical. This work was funded by grant GM025690 to E.U.S. from the US National Institutes of Health. We acknowledge the Neurospora Genome Project and the Fungal Genetic Stock Center for providing materials.
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology