Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications Journal Article
| Authors: | Nakagawa, H.; Lee, J. K.; Hurwitz, J.; Allshire, R. C.; Nakayama, J. I.; Grewal, S. I. S.; Tanaka, K.; Murakami, Y. |
| Article Title: | Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications |
| 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 α-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. |
| Keywords: | controlled study; unclassified drug; promoter region; sequence analysis; dna-binding proteins; nonhuman; phenotype; chromosomal proteins, non-histone; protein; protein binding; genotype; drosophila; microfilament proteins; transcription factors; eukaryota; histone; gene disruption; immunoprecipitation; autoantigens; binding sites; gene silencing; saccharomyces cerevisiae proteins; eukaryotic cell; sequence homology; histones; mutagenesis; protein methylation; deacetylation; centromere; heterochromatin; schizosaccharomyces; schizosaccharomyces pombe proteins; mutagenesis, insertional; protein modification; schizosaccharomyces pombe; fission yeast; fungal proteins; histone modification; priority journal; article; cenp-b; centromere protein b; protein abp1; protein cbh1; protein cbh2 |
| Journal Title: | Genes and Development |
| Volume: | 16 |
| Issue: | 14 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2002-07-15 |
| Start Page: | 1766 |
| End Page: | 1778 |
| Language: | English |
| DOI: | 10.1101/gad.997702 |
| PUBMED: | 12130537 |
| PROVIDER: | scopus |
| PMCID: | PMC186399 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work