Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase

  title={Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase},
  author={Shin-ichiro Imai and Christopher M. Armstrong and Matt Kaeberlein and Leonard P Guarente},
Yeast Sir2 is a heterochromatin component that silences transcription at silent mating loci, telomeres and the ribosomal DNA, and that also suppresses recombination in the rDNA and extends replicative life span. Mutational studies indicate that lysine 16 in the amino-terminal tail of histone H4 and lysines 9, 14 and 18 in H3 are critically important in silencing, whereas lysines 5, 8 and 12 of H4 have more redundant functions. Lysines 9 and 14 of histone H3 and lysines 5, 8 and 16 of H4 are… 

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

It is shown that the level of H3-K79 methylation is low at all Sir-dependent silenced loci but not at other transcriptionally repressed regions, and that silencing proteins block the ability of Dot1 to methylate histone H3.

Redundant Roles for Histone H3 N-Terminal Lysine Residues in Subtelomeric Gene Repression in Saccharomyces cerevisiae

It is proposed that acetylation and methylation of histone H3 N-terminal lysine residues act as redundant mechanisms to demarcate regions of euchromatin from heterochromatin.

Interplay between histone deacetylase SIR-2, linker histone H1 and histone methyltransferases in heterochromatin formation

The interplay between SIR-2, H1 histone and histone methyltransferases in modulation of chromatin structure is discussed and shown to be functionally related in heterochromatin formation contributing to fertility and embryogenesis.

Histone deacetylation by Sir2 generates a transcriptionally repressed nucleoprotein complex

The findings suggest that deacetylation by Sir2 causes a conformational change or rearrangement of histones into a transcriptionally repressive chromatin structure.

A dual role of H4K16 acetylation in the establishment of yeast silent chromatin

It is concluded that acetylated H 4K16 has a dual role in silencing: it recruits Sir2‐4 and repels Sir3, and the deacetylation of H4K16ac by Sir2 actively promotes the high‐affinity binding of the SIR holocomplex.

Steps in Assembly of Silent Chromatin in Yeast: Sir3-Independent Binding of a Sir2/Sir4 Complex to Silencers and Role for Sir2-Dependent Deacetylation

A stepwise model for the assembly of silent chromatin domains in Saccharomyces cerevisiae is supported by results at the rDNA repeats and at the Sir2/Sir4 complex.



Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern

It is reported that, as observed in the facultative heterochromatin of the inactive X chromosome in female mammalian cells, histones H3 and H4 in chromatin spanning the transcriptionally silenced mating-type cassettes of the yeast Saccharomyces cerevisiae are hypoacetylated relative to histones F3 and F4 of transcriptionally active regions of the genome.

Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.

The hypothesis that silencing in yeast results from heterochromatin formation is fortified and it is argued that the silencing proteins participate in this formation.

Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast

It is reported that histone H3 is required for full repression at yeast telomeres and at partially disabled silent mating loci, and that the acetylatable lysine residues of H3 play an important role in silencing.

Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.

It is proposed that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon and deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDNs.

An unusual form of transcriptional silencing in yeast ribosomal DNA.

A novel form of transcriptional silencing in S. cerevisiae in the ribosomal DNA (rDNA) tandem array is identified, suggesting that a specific chromatin structure in rDNA down-regulates polymerase II promoters.

Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae

It is proposed that Sir proteins act with Hdf1 to alter broken DNA ends to create an inactivated chromatin structure that is essential for the rejoining of DNA ends.