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PMID: 12130537 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications.

Genes & development ·Vol. 16 ·No. 14 ·2002-07-15 ·Pages 1766-78

Nakagawa H, Lee JK, Hurwitz J, Allshire RC, Nakayama J, Grewal SI, Tanaka K, Murakami Y

Abstract

Heterochromatin is a functionally important chromosomal component, especially at centromeres. In fission yeast, conserved heterochromatin-specific modifications of the histone H3 tail, involving deacetylation of Lys 9 and Lys 14 and subsequent methylation of Lys 9, promote the recruitment of a heterochromatin protein, Swi6, a homolog of the Drosophila heterochromatin protein 1. However, the primary determinants of the positioning of heterochromatin are still unclear. The fission yeast proteins Abp1, Cbh1, and Cbh2 are homologs of the human protein CENP-B that bind to centromeric alpha-satellite DNA and associate with centromeric heterochromatin. We show that the CENP-B homologs are functionally redundant at centromeres, and that Abp1 binds specifically to centromeric heterochromatin. In the absence of Abp1 or Cbh1, the centromeric association of Swi6 is diminished, resulting in a decrease in silencing of the region. CENP-B-homolog double disruptants show a synergistic reduction of Swi6 at centromeric heterochromatin, indicating that the three proteins are functionally redundant in the recruitment of Swi6. Furthermore, using chromatin immunoprecipitation assays, we show that disruption of CENP-B homologs causes a decrease in heterochromatin-specific modifications of histone H3. These results indicate that the CENP-B homologs act as site-specific nucleation factors for the formation of centromeric heterochromatin by heterochromatin-specific modifications of histone tails.

MeSH Terms
Autoantigens Binding Sites Centromere/metabolism Centromere Protein B Chromosomal Proteins, Non-Histone/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Fungal Proteins/genetics,metabolism Gene Silencing Heterochromatin/metabolism Histones/metabolism Microfilament Proteins Mutagenesis Mutagenesis, Insertional Phenotype Saccharomyces cerevisiae Proteins/genetics,metabolism Schizosaccharomyces/genetics,metabolism Schizosaccharomyces pombe Proteins Transcription Factors/genetics,metabolism
Chemicals
ABP1 protein, S cerevisiae Autoantigens Cbh2 protein, S pombe Centromere Protein B Chromosomal Proteins, Non-Histone DNA-Binding Proteins Fungal Proteins Heterochromatin Histones Microfilament Proteins SWI6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins Transcription Factors ura4 protein, S pombe
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nakagawa Hiromi
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Lee Joon-Kyu
Hurwitz Jerard
Allshire Robin C
Nakayama Jun-Ichi
Grewal Shiv I S
Tanaka Katsunori
Murakami Yota
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.997702
Published
2002-07-15
Pages
1766-78
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC186399
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.997702 PMC Full Text View journal details
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