Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing

Elizabeth T. Wiles; Kevin J. McNaught; Gurmeet Kaur; Jeanne M.L. Selker; Tereza Ormsby; L. Aravind; Eric U. Selker

doi:10.1073/pnas.1918776117

Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing

Elizabeth T. Wiles, Kevin J. McNaught, Gurmeet Kaur, Jeanne M.L. Selker, Tereza Ormsby, L. Aravind, Eric U. Selker

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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
Article number	A61
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	21
DOIs	https://doi.org/10.1073/pnas.1918776117
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
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

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10.1073/pnas.1918776117

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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.",

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AU - McNaught, Kevin J.

AU - Kaur, Gurmeet

AU - Selker, Jeanne M.L.

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AU - Aravind, L.

AU - Selker, Eric U.

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AB - 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.

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KW - Facultative heterochromatin

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Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing

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