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PMID: 12574507 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 4 ·2003-02-18 ·Pages 1820-5

Ng HH, Ciccone DN, Morshead KB, Oettinger MA, Struhl K

Abstract

Methylation of lysine-79 (K79) within the globular domain of histone H3 by Dot1 methylase is important for transcriptional silencing and for association of the Sir silencing proteins in yeast. Here, we show that the level of H3-K79 methylation is low at all Sir-dependent silenced loci but not at other transcriptionally repressed regions. Hypomethylation of H3-K79 at the telomeric and silent mating-type loci, but not the ribosomal DNA, requires the Sir proteins. Overexpression of Sir3 concomitantly extends the domain of Sir protein association and H3-K79 hypomethylation at telomeres. In mammalian cells, H3-K79 methylation is found at loci that are active for V(D)J recombination, but not at recombinationally inactive loci that are heterochromatic. These results suggest that H3-K79 methylation is an evolutionarily conserved marker of active chromatin regions, and that silencing proteins block the ability of Dot1 to methylate histone H3. Further, they suggest that Sir proteins preferentially bind chromatin with hypomethylated H3-K79 and then block H3-K79 methylation. This positive feedback loop, and the reverse loop in which H3-K79 methylation weakens Sir protein association and leads to further methylation, suggests a model for position-effect variegation.

MeSH Terms
Acetylation Animals Chromatin/metabolism DNA, Ribosomal/genetics Gene Silencing Histones/chemistry,genetics,metabolism Lysine/metabolism Methylation Mice Saccharomyces cerevisiae/genetics Transcription, Genetic
Chemicals
Chromatin DNA, Ribosomal Histones Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ng Huck Hui
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Ciccone David N
Morshead Katrina B
Oettinger Marjorie A
Struhl Kevin
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0437846100
Published
2003-02-18
Epub
2003-00-06
Pages
1820-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC149917
Subset
IM
Grants
NIGMS NIH HHS · R01 GM048026 · United States
NIGMS NIH HHS · R01 GM053720 · United States
NIGMS NIH HHS · GM 48026 · United States
NIGMS NIH HHS · GM 53720 · United States
External Links
PubMed source DOI: 10.1073/pnas.0437846100 PMC Full Text View journal details
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