The Polycomb Group Mutant esc Leads to Augmented Levels of Paused Pol II in the Drosophila Embryo

Vivek S. Chopra; David A. Hendrix; Leighton J. Core; Chiahao Tsui; John T. Lis; Michael Levine

doi:10.1016/j.molcel.2011.05.009

The Polycomb Group Mutant esc Leads to Augmented Levels of Paused Pol II in the Drosophila Embryo

Vivek S. Chopra, David A. Hendrix, Leighton J. Core, Chiahao Tsui, John T. Lis, Michael Levine

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

40 Scopus citations

Abstract

Many developmental control genes contain paused RNA polymerase II (Pol II) and are thereby " poised" for rapid and synchronous activation in the early Drosophila embryo. Evidence is presented that Polycomb group (PcG) repressors can influence paused Pol II. ChIP-Seq and GRO-Seq assays were used to determine the genome-wide distributions of Pol II, H3K27me3, and H3K4me3 in extra sex combs (esc) mutant embryos. ESC is a key component of the Polycomb repressive complex 2 (PRC2), which mediates H3K27me3 modification. Enhanced Pol II occupancy is observed for thousands of genes in esc mutant embryos, including genes not directly regulated by PRC2. Thus, it would appear that silent genes lacking promoter-associated paused Pol II in wild-type embryos are converted into " poised" genes with paused Pol II in esc mutants. We suggest that this conversion of silent genes into poised genes might render differentiated cell types susceptible to switches in identity in PcG mutants.

Original language	English (US)
Pages (from-to)	837-844
Number of pages	8
Journal	Molecular Cell
Volume	42
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2011.05.009
State	Published - Jun 24 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1016/j.molcel.2011.05.009

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title = "The Polycomb Group Mutant esc Leads to Augmented Levels of Paused Pol II in the Drosophila Embryo",

abstract = "Many developmental control genes contain paused RNA polymerase II (Pol II) and are thereby {"} poised{"} for rapid and synchronous activation in the early Drosophila embryo. Evidence is presented that Polycomb group (PcG) repressors can influence paused Pol II. ChIP-Seq and GRO-Seq assays were used to determine the genome-wide distributions of Pol II, H3K27me3, and H3K4me3 in extra sex combs (esc) mutant embryos. ESC is a key component of the Polycomb repressive complex 2 (PRC2), which mediates H3K27me3 modification. Enhanced Pol II occupancy is observed for thousands of genes in esc mutant embryos, including genes not directly regulated by PRC2. Thus, it would appear that silent genes lacking promoter-associated paused Pol II in wild-type embryos are converted into {"} poised{"} genes with paused Pol II in esc mutants. We suggest that this conversion of silent genes into poised genes might render differentiated cell types susceptible to switches in identity in PcG mutants.",

author = "Chopra, {Vivek S.} and Hendrix, {David A.} and Core, {Leighton J.} and Chiahao Tsui and Lis, {John T.} and Michael Levine",

note = "Funding Information: We thank Elim Biopharm, Inc. (Hayward, CA) and L. Tonkin (UC Berkeley) for high-throughput DNA sequencing. J. Choi and K. Hermens (UC Berkeley) provided valuable help with library quantification. We are particularly grateful to G. Struhl and J. Simon for providing esc mutant stocks, I. Hariharan for the heat shock GAL4 stock, the Bloomington Stock Center for providing UAS-Abd-B flies, and M. O'Connor for the wit plasmid. Thanks to P. Paliwal for support and help with the western blot assays. Thanks to J. M{\"u}ller, D.S. Rokhsar, and Levine lab members for helpful discussions and feedback. We also thank K. Adelman for sharing the list of top quartile paused genes. This study was funded by grants from the NIH (GM34431) to M.L. and (HG004845) to J.T.L. ",

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AU - Chopra, Vivek S.

AU - Hendrix, David A.

AU - Core, Leighton J.

AU - Tsui, Chiahao

AU - Lis, John T.

AU - Levine, Michael

N1 - Funding Information: We thank Elim Biopharm, Inc. (Hayward, CA) and L. Tonkin (UC Berkeley) for high-throughput DNA sequencing. J. Choi and K. Hermens (UC Berkeley) provided valuable help with library quantification. We are particularly grateful to G. Struhl and J. Simon for providing esc mutant stocks, I. Hariharan for the heat shock GAL4 stock, the Bloomington Stock Center for providing UAS-Abd-B flies, and M. O'Connor for the wit plasmid. Thanks to P. Paliwal for support and help with the western blot assays. Thanks to J. Müller, D.S. Rokhsar, and Levine lab members for helpful discussions and feedback. We also thank K. Adelman for sharing the list of top quartile paused genes. This study was funded by grants from the NIH (GM34431) to M.L. and (HG004845) to J.T.L.

PY - 2011/6/24

Y1 - 2011/6/24

N2 - Many developmental control genes contain paused RNA polymerase II (Pol II) and are thereby " poised" for rapid and synchronous activation in the early Drosophila embryo. Evidence is presented that Polycomb group (PcG) repressors can influence paused Pol II. ChIP-Seq and GRO-Seq assays were used to determine the genome-wide distributions of Pol II, H3K27me3, and H3K4me3 in extra sex combs (esc) mutant embryos. ESC is a key component of the Polycomb repressive complex 2 (PRC2), which mediates H3K27me3 modification. Enhanced Pol II occupancy is observed for thousands of genes in esc mutant embryos, including genes not directly regulated by PRC2. Thus, it would appear that silent genes lacking promoter-associated paused Pol II in wild-type embryos are converted into " poised" genes with paused Pol II in esc mutants. We suggest that this conversion of silent genes into poised genes might render differentiated cell types susceptible to switches in identity in PcG mutants.

AB - Many developmental control genes contain paused RNA polymerase II (Pol II) and are thereby " poised" for rapid and synchronous activation in the early Drosophila embryo. Evidence is presented that Polycomb group (PcG) repressors can influence paused Pol II. ChIP-Seq and GRO-Seq assays were used to determine the genome-wide distributions of Pol II, H3K27me3, and H3K4me3 in extra sex combs (esc) mutant embryos. ESC is a key component of the Polycomb repressive complex 2 (PRC2), which mediates H3K27me3 modification. Enhanced Pol II occupancy is observed for thousands of genes in esc mutant embryos, including genes not directly regulated by PRC2. Thus, it would appear that silent genes lacking promoter-associated paused Pol II in wild-type embryos are converted into " poised" genes with paused Pol II in esc mutants. We suggest that this conversion of silent genes into poised genes might render differentiated cell types susceptible to switches in identity in PcG mutants.

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The Polycomb Group Mutant esc Leads to Augmented Levels of Paused Pol II in the Drosophila Embryo

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