Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth. Basenko, E. Y., Sasaki, T., Ji, L., Prybol, C. J., Burckhardt, R. M., Schmitz, R. J., & Lewis, Z. A. Proc Natl Acad Sci U S A, 112(46):E6339-48, 2015. 1091-6490 Basenko, Evelina Y Sasaki, Takahiko Ji, Lexiang Prybol, Cameron J Burckhardt, Rachel M Schmitz, Robert J Lewis, Zachary A Orcid: 0000-0002-1735-8266 P01 GM068087/GM/NIGMS NIH HHS/United States R00 GM100000/GM/NIGMS NIH HHS/United States P01GM68087/GM/NIGMS NIH HHS/United States R00GM100000/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2015/11/19 Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6339-48. doi: 10.1073/pnas.1511377112. Epub 2015 Nov 2.doi abstract bibtex H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress.
@article{RN37,
author = {Basenko, E. Y. and Sasaki, T. and Ji, L. and Prybol, C. J. and Burckhardt, R. M. and Schmitz, R. J. and Lewis, Z. A.},
title = {Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth},
journal = {Proc Natl Acad Sci U S A},
volume = {112},
number = {46},
pages = {E6339-48},
note = {1091-6490
Basenko, Evelina Y
Sasaki, Takahiko
Ji, Lexiang
Prybol, Cameron J
Burckhardt, Rachel M
Schmitz, Robert J
Lewis, Zachary A
Orcid: 0000-0002-1735-8266
P01 GM068087/GM/NIGMS NIH HHS/United States
R00 GM100000/GM/NIGMS NIH HHS/United States
P01GM68087/GM/NIGMS NIH HHS/United States
R00GM100000/GM/NIGMS NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2015/11/19
Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6339-48. doi: 10.1073/pnas.1511377112. Epub 2015 Nov 2.},
abstract = {H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress.},
keywords = {*DNA Damage
Fungal Proteins/genetics/*metabolism
*Genome, Fungal
Heterochromatin/genetics/metabolism
Histones/genetics/*metabolism
Methylation
Multienzyme Complexes/genetics/metabolism
Neurospora crassa/genetics/*metabolism
Protein Methyltransferases/genetics/*metabolism
H3K27me3
H3K9me3
Polycomb
genotoxic stress
heterochromatin},
ISSN = {0027-8424 (Print)
0027-8424},
DOI = {10.1073/pnas.1511377112},
year = {2015},
type = {Journal Article}
}
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A."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Basenko"],"firstnames":["E.","Y."],"suffixes":[]},{"propositions":[],"lastnames":["Sasaki"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Ji"],"firstnames":["L."],"suffixes":[]},{"propositions":[],"lastnames":["Prybol"],"firstnames":["C.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Burckhardt"],"firstnames":["R.","M."],"suffixes":[]},{"propositions":[],"lastnames":["Schmitz"],"firstnames":["R.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Lewis"],"firstnames":["Z.","A."],"suffixes":[]}],"title":"Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth","journal":"Proc Natl Acad Sci U S A","volume":"112","number":"46","pages":"E6339-48","note":"1091-6490 Basenko, Evelina Y Sasaki, Takahiko Ji, Lexiang Prybol, Cameron J Burckhardt, Rachel M Schmitz, Robert J Lewis, Zachary A Orcid: 0000-0002-1735-8266 P01 GM068087/GM/NIGMS NIH HHS/United States R00 GM100000/GM/NIGMS NIH HHS/United States P01GM68087/GM/NIGMS NIH HHS/United States R00GM100000/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2015/11/19 Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6339-48. doi: 10.1073/pnas.1511377112. 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A.},\r\n title = {Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth},\r\n journal = {Proc Natl Acad Sci U S A},\r\n volume = {112},\r\n number = {46},\r\n pages = {E6339-48},\r\n note = {1091-6490\r\nBasenko, Evelina Y\r\nSasaki, Takahiko\r\nJi, Lexiang\r\nPrybol, Cameron J\r\nBurckhardt, Rachel M\r\nSchmitz, Robert J\r\nLewis, Zachary A\r\nOrcid: 0000-0002-1735-8266\r\nP01 GM068087/GM/NIGMS NIH HHS/United States\r\nR00 GM100000/GM/NIGMS NIH HHS/United States\r\nP01GM68087/GM/NIGMS NIH HHS/United States\r\nR00GM100000/GM/NIGMS NIH HHS/United States\r\nJournal Article\r\nResearch Support, N.I.H., Extramural\r\nResearch Support, Non-U.S. Gov't\r\nUnited States\r\n2015/11/19\r\nProc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6339-48. doi: 10.1073/pnas.1511377112. 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