Abstract
Methylation of histone H3 lysine 27 (H3K27) is widely recognized as a transcriptionally repressive chromatin modification but the mechanism of repression remains unclear. We devised and implemented a forward genetic scheme to identify factors required for H3K27 methylation-mediated silencing in the filamentous fungus Neurospora crassa and identified a bromo-adjacent homology (BAH)-plant homeodomain (PHD)-containing protein, EPR-1 (effector of polycomb repression 1; NCU07505). EPR-1 associates with H3K27-methylated chromatin, and loss of EPR-1 de-represses H3K27- methylated genes without loss of H3K27 methylation. EPR-1 is not fungal-specific; orthologs of EPR-1 are present in a diverse array of eukaryotic lineages, suggesting an ancestral EPR-1 was a component of a primitive Polycomb repression pathway.
Original language | English |
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Article number | A61 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 117 |
Issue number | 21 |
DOIs | |
State | Published - May 26 2020 |
Externally published | Yes |
Funding
ACKNOWLEDGMENTS. We thank S. De Silva and C. Musselman (University of Colorado Anschutz Medical Campus), and C. Petell and B. Strahl (University of North Carolina School of Medicine) for their significant efforts to characterize the binding specificity of EPR-1 in vitro; S. Honda (University of Fukui) for providing Neurospora crassa strains utilized in fluorescence microscopy experiments; J. Lyle, A. Leiferman, and N. Meyers for help mapping the UV-generated mutants; A. Harvey for help with preliminary microscopy experiments; and A. Zemper for chicken anti-GFP and goat anti-chicken HRP antibodies. This work was funded by National Institutes of Health Grants GM127142 and GM093061 (to E.U.S.) and HD007348 (for partial support of K.J.M.); and the American Heart Association Grant 14POST20450071 (for partial support of E.T.W.). G.K. and L.A. were supported by the Intramural Research Program of the National Library of Medicine.
Funders | Funder number |
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National Institutes of Health | GM093061, HD007348 |
National Institute of General Medical Sciences | R35GM127142 |
U.S. National Library of Medicine | |
American Heart Association | 14POST20450071 |
Keywords
- Epigenetics
- Facultative heterochromatin
- H3K27 methylation
- Histone reader
- Polycomb repressive complex