Mediator influences telomeric silencing and cellular life span.

• The Mediator complex is required for the regulated transcription of nearly all RNA polymerase II-dependent genes. Here we demonstrate a new role for Mediator which appears to be separate from its function as a transcriptional coactivator. Mediator associates directly with heterochromatin at telomeres and influences the exact boundary between active and inactive chromatin. Loss of the Mediator Med5 subunit or mutations in Med7 cause a depletion of the complex from regions located near subtelomeric X elements, which leads to a change in the balance between the Sir2 and Sas2 proteins. These changes in turn result in increased levels of H4K16 acetylation near telomeres and in desilencing of subtelomeric genes. Increases in H4K16 acetylation have been observed at telomeres in aging cells. In agreement with this observation, we found that the loss of MED5 leads to shortening of the Saccharomyces cerevisiae (budding yeast) replicative life span.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

Nyckelord

Cell Aging

physiology

Gene Expression Regulation

Fungal

Gene Silencing

Histone Acetyltransferases

genetics

metabolism

Histones

metabolism

Mediator Complex

genetics

metabolism

Mutation

Protein Subunits

genetics

metabolism

Saccharomyces cerevisiae

physiology

Saccharomyces cerevisiae Proteins

genetics

metabolism

Silent Information Regulator Proteins

Saccharomyces cerevisiae

genetics

metabolism

Sirtuin 2

genetics

metabolism

Telomere

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)