Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors

Jennifer Carlson; Thane Swisse; Charles Smith; Huai Deng

doi:10.1002/dvg.23290

Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors

Jennifer Carlson, Thane Swisse, Charles Smith, Huai Deng

Biology (Duluth)

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

3 Scopus citations

Abstract

The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the effects of their Drosophila homologs (dKeap1 and CncC) on position effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of w ^m4 and Sb ^V PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.

Original language	English (US)
Article number	e23290
Journal	Genesis
Volume	57
Issue number	4
DOIs	https://doi.org/10.1002/dvg.23290
State	Published - Apr 2019

Bibliographical note

Funding Information:
We thank Dirk Bohmann, Osamu Shimmi, Kristen Johansen, and Lori Wallrath for generously providing Drosophila stocks. We thank Lori Wallrath for discussions and suggestions. We thank members of Deng laboratory for discussions and critical reading of the manuscript. This work was supported by National Institutes of Health grant (GM128143) to H.D. and by the start-up funding from the University of Minnesota Duluth to H.D.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

Keap1-Nrf2
dKeap1-CncC
heterochromatin
oxidative and xenobiotic responses
position effect variegation

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10.1002/dvg.23290

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@article{1ab997faf38a4fa3bd4bb972341519f2,

title = "Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors",

abstract = " The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the effects of their Drosophila homologs (dKeap1 and CncC) on position effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of w m4 and Sb V PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.",

keywords = "Keap1-Nrf2, dKeap1-CncC, heterochromatin, oxidative and xenobiotic responses, position effect variegation",

author = "Jennifer Carlson and Thane Swisse and Charles Smith and Huai Deng",

note = "Funding Information: We thank Dirk Bohmann, Osamu Shimmi, Kristen Johansen, and Lori Wallrath for generously providing Drosophila stocks. We thank Lori Wallrath for discussions and suggestions. We thank members of Deng laboratory for discussions and critical reading of the manuscript. This work was supported by National Institutes of Health grant (GM128143) to H.D. and by the start-up funding from the University of Minnesota Duluth to H.D. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

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AU - Carlson, Jennifer

AU - Swisse, Thane

AU - Smith, Charles

AU - Deng, Huai

N1 - Funding Information: We thank Dirk Bohmann, Osamu Shimmi, Kristen Johansen, and Lori Wallrath for generously providing Drosophila stocks. We thank Lori Wallrath for discussions and suggestions. We thank members of Deng laboratory for discussions and critical reading of the manuscript. This work was supported by National Institutes of Health grant (GM128143) to H.D. and by the start-up funding from the University of Minnesota Duluth to H.D. Publisher Copyright: © 2019 Wiley Periodicals, Inc.

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N2 - The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the effects of their Drosophila homologs (dKeap1 and CncC) on position effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of w m4 and Sb V PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.

AB - The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the effects of their Drosophila homologs (dKeap1 and CncC) on position effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of w m4 and Sb V PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.

KW - Keap1-Nrf2

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KW - heterochromatin

KW - oxidative and xenobiotic responses

KW - position effect variegation

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U2 - 10.1002/dvg.23290

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M3 - Letter

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SN - 1526-954X

VL - 57

JO - Genesis

JF - Genesis

IS - 4

M1 - e23290

ER -

Regulation of position effect variegation at pericentric heterochromatin by Drosophila Keap1-Nrf2 xenobiotic response factors

Abstract

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