The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa

Colleen C. Mumford; Hideki Tanizawa; Elizabeth T. Wiles; Kevin J. McNaught; Kirsty Jamieson; Kenta Tsukamoto; Eric U. Selker

doi:10.1073/pnas.2404770121

The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa

Colleen C. Mumford
, Hideki Tanizawa
, Elizabeth T. Wiles
, Kevin J. McNaught
, Kirsty Jamieson
, Kenta Tsukamoto
, Eric U. Selker

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

1 Scopus citations

Abstract

Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in Neurospora crassa and identified three previously uncharacterized genes that are important for silencing: sds3 (NCU01599), rlp1 (RPD3L protein 1; NCU09007), and rlp2 (RPD3L protein 2; NCU02898). We found that SDS3, RLP1, and RLP2 associate with N. crassa homologs of the Saccharomyces cerevisiae Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in N. crassa, and perhaps in other organisms.

Original language	English
Article number	e2404770121
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	121
Issue number	32
DOIs	https://doi.org/10.1073/pnas.2404770121
State	Published - Aug 6 2024
Externally published	Yes

Funding

ACKNOWLEDGMENTS. We thank J. Yoo and D. Keahi for help with constructing tagged strains and coimmunoprecipitation experiments, M. Salemi at the University of California, Davis Proteomics Core Facility for the mass spectrometry work, University of Oregon Genomics and Cell Characterization Core Facility for Illumina sequencing, and J. Selker and K. Noma for their helpful comments on the manuscript.This work was funded by the National Institute of General Medical Sciences (GM127142 and GM093061 to E.U.S.).

Keywords

H3K27 methylation
epigenetics
histone modification
polycomb repressive complex
transcriptional silencing

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10.1073/pnas.2404770121

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Mumford, C. C., Tanizawa, H., Wiles, E. T., McNaught, K. J., Jamieson, K., Tsukamoto, K., & Selker, E. U. (2024). The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa. Proceedings of the National Academy of Sciences of the United States of America, 121(32), Article e2404770121. https://doi.org/10.1073/pnas.2404770121

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abstract = "Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in Neurospora crassa and identified three previously uncharacterized genes that are important for silencing: sds3 (NCU01599), rlp1 (RPD3L protein 1; NCU09007), and rlp2 (RPD3L protein 2; NCU02898). We found that SDS3, RLP1, and RLP2 associate with N. crassa homologs of the Saccharomyces cerevisiae Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in N. crassa, and perhaps in other organisms.",

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The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa. / Mumford, Colleen C.; Tanizawa, Hideki; Wiles, Elizabeth T. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 121, No. 32, e2404770121, 06.08.2024.

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

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T1 - The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa

AU - Mumford, Colleen C.

AU - Tanizawa, Hideki

AU - Wiles, Elizabeth T.

AU - McNaught, Kevin J.

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AU - Tsukamoto, Kenta

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N2 - Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in Neurospora crassa and identified three previously uncharacterized genes that are important for silencing: sds3 (NCU01599), rlp1 (RPD3L protein 1; NCU09007), and rlp2 (RPD3L protein 2; NCU02898). We found that SDS3, RLP1, and RLP2 associate with N. crassa homologs of the Saccharomyces cerevisiae Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in N. crassa, and perhaps in other organisms.

AB - Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in Neurospora crassa and identified three previously uncharacterized genes that are important for silencing: sds3 (NCU01599), rlp1 (RPD3L protein 1; NCU09007), and rlp2 (RPD3L protein 2; NCU02898). We found that SDS3, RLP1, and RLP2 associate with N. crassa homologs of the Saccharomyces cerevisiae Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in N. crassa, and perhaps in other organisms.

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KW - epigenetics

KW - histone modification

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KW - transcriptional silencing

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ER -

The RPD3L deacetylation complex is required for facultative heterochromatin repression in Neurospora crassa

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