The ACF chromatin remodeling complex is essential for Polycomb repression

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

doi:10.7554/eLife.77595

The ACF chromatin remodeling complex is essential for Polycomb repression

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

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

9 Scopus citations

Abstract

Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus Neurospora crassa. We found that the N. crassa homologs of ISWI (NCU03875) and ACF1 (NCU00164) are required for repression of a subset of H3K27 methylated genes and that they form an ACF chromatin remodeling complex. This ACF complex interacts with chromatin throughout the genome, yet association with facultative heterochromatin is specifically promoted by the H3K27 methyltransferase, SET-7. H3K27-methylated genes that are upregulated when iswi or acf1 are deleted show a downstream shift of the +1 nucleosome, suggesting that proper nucleosome positioning is critical for repression of facultative heterochromatin. Our findings support a direct role for the ACF complex in Polycomb repression.

Original language	English
Journal	eLife
DOIs	https://doi.org/10.7554/eLife.77595
State	Published - Mar 2022
Externally published	Yes

Funding

We thank J. Lyle and R. Morse for help in genetic mapping of UV-generated mutants; V. Bicocca for performing initial experiments characterizing ISWI and for comments on the manuscript; and J. McKnight and L. McKnight for providing guidance and reagents for rapid MNase digestion. We also thank T. Bailey, D. Donovan, L. McKnight, and K. Noma for helpful comments on the manuscript. This work was funded by the National Institute of General Medical Sciences (GM127142 and GM093061 to E.U.S.), American Heart Association (14POST20450071 to E.T.W.), and K.J.M. was partially supported by the National Institutes of Health (HD007348).

Funders	Funder number
National Institutes of Health	HD007348
National Institute of General Medical Sciences	GM093061, R35GM127142
American Heart Association	14POST20450071

Keywords

ACF
H3K27 methylation
ISWI
Isw2
PRC2
chromatin remodeler
facultative heterochromatin
nucleosome positioning

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10.7554/eLife.77595

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title = "The ACF chromatin remodeling complex is essential for Polycomb repression",

abstract = "Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus Neurospora crassa. We found that the N. crassa homologs of ISWI (NCU03875) and ACF1 (NCU00164) are required for repression of a subset of H3K27 methylated genes and that they form an ACF chromatin remodeling complex. This ACF complex interacts with chromatin throughout the genome, yet association with facultative heterochromatin is specifically promoted by the H3K27 methyltransferase, SET-7. H3K27-methylated genes that are upregulated when iswi or acf1 are deleted show a downstream shift of the +1 nucleosome, suggesting that proper nucleosome positioning is critical for repression of facultative heterochromatin. Our findings support a direct role for the ACF complex in Polycomb repression.",

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year = "2022",

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AU - Wiles, Elizabeth T.

AU - Mumford, Colleen C.

AU - McNaught, Kevin J.

AU - Tanizawa, Hideki

AU - Selker, Eric U.

PY - 2022/3

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N2 - Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus Neurospora crassa. We found that the N. crassa homologs of ISWI (NCU03875) and ACF1 (NCU00164) are required for repression of a subset of H3K27 methylated genes and that they form an ACF chromatin remodeling complex. This ACF complex interacts with chromatin throughout the genome, yet association with facultative heterochromatin is specifically promoted by the H3K27 methyltransferase, SET-7. H3K27-methylated genes that are upregulated when iswi or acf1 are deleted show a downstream shift of the +1 nucleosome, suggesting that proper nucleosome positioning is critical for repression of facultative heterochromatin. Our findings support a direct role for the ACF complex in Polycomb repression.

AB - Establishing and maintaining appropriate gene repression is critical for the health and development of multicellular organisms. Histone H3 lysine 27 (H3K27) methylation is a chromatin modification associated with repressed facultative heterochromatin, but the mechanism of this repression remains unclear. We used a forward genetic approach to identify genes involved in transcriptional silencing of H3K27-methylated chromatin in the filamentous fungus Neurospora crassa. We found that the N. crassa homologs of ISWI (NCU03875) and ACF1 (NCU00164) are required for repression of a subset of H3K27 methylated genes and that they form an ACF chromatin remodeling complex. This ACF complex interacts with chromatin throughout the genome, yet association with facultative heterochromatin is specifically promoted by the H3K27 methyltransferase, SET-7. H3K27-methylated genes that are upregulated when iswi or acf1 are deleted show a downstream shift of the +1 nucleosome, suggesting that proper nucleosome positioning is critical for repression of facultative heterochromatin. Our findings support a direct role for the ACF complex in Polycomb repression.

KW - ACF

KW - H3K27 methylation

KW - ISWI

KW - Isw2

KW - PRC2

KW - chromatin remodeler

KW - facultative heterochromatin

KW - nucleosome positioning

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AN - SCOPUS:85127401301

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JO - eLife

JF - eLife

ER -

The ACF chromatin remodeling complex is essential for Polycomb repression

Abstract

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Keywords

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