Old School: Distant relatives share gene-regulating mechanism (Evolution; Chromatin structure)
Authors: Davenport R. John 
Published: August 2003

Eons of innovation can't stamp out tried-and-true ways. A method for bundling DNA and controlling access to its information is more ancient than previously thought, according to new work. The findings suggest that the mechanism, which governs life-span in yeast, operates in distant relatives as well.

Three years ago, Leonard Guarente and co-workers at the Massachusetts Institute of Technology found that yeast with extra Sir2 protein lived longer than normal (see
Kaeberlein Perspective
). Sir2 removes chemical tags called acetyl groups from proteins that compact DNA. Without acetyl groups, these proteins, called histones, block transcription--the process in which protein machinery produces messenger RNA. By this means, Sir2 shuts off genes in particular regions of the genome--and it also protects those sections from reshuffling, thereby lengthening yeast life-span. Sir2 genes also exist in archaea, a group of life that split off from eukaryotes--organisms whose cells have a nucleus--2 billion years ago. Archaea have a taste for extreme environments and resemble bacteria physically, although they're more closely related to eukaryotes.

Bell and colleagues wondered whether archaeal Sir2, like its yeast counterpart, alters DNA packing and gene expression. The researchers first looked for protein partners of Sir2 in an archaeon called
Sulfolobus solfataricus
. They attached Sir2 to tiny beads, added the contents of
S. solfataricus
cells, and looked for proteins that stuck. One did, which they called Alba.

Additional experiments suggest that Sir2 and Alba constitute part of a system that turns genes on and off. First, the researchers showed that Alba can carry acetyl groups. Then they investigated whether acetylation of Alba alters the transcription of a sample gene in a test tube. Like histones, acetylated Alba binds more loosely to DNA and hinders transcription machinery less effectively than the unacetylated protein does. Sir2 appears to remove acetyl groups from Alba as well: Adding it to the reaction mixture turns the test gene off. The results suggest that archaeal Sir2 performs biochemical tasks similar to those undertaken by the yeast protein.

Although researchers knew that the bare-bones transcriptional equipment of archaea and eukaryotes was similar, they previously thought that only eukaryotes control genes by altering DNA packing. The new study suggests that archaea do it too. Scientists might need to "rewrite the prokaryotic versus eukaryotic divide in transcriptional regulation," says study author and biochemist Stephen Bell of the Medical Research Council in Cambridge, U.K. Many eukaryotes have proteins that are related to Alba, he adds, so "we may have identified a novel player in eukaryotic Sir2 regulation as well as in archaea."

"The fact that this [Sir2-mediated deacetylation mechanism] is so old and has been preserved along these two distinct lineages means that it's fundamental," says Guarente. Sir2's impact on life-span also stretches beyond yeast--it extends life in worms as well--although the means by which it confers longevity likely differ from one organism to the next. No one knows whether archaeal Sir2 will uncover any secrets of the aging process, but it seems to have revealed the age of its gene-regulating power.

--R. John Davenport

S. D. Bell, C. H. Botting, B. N. Wardleworth, S. P. Jackson, M. F. White, The interaction of Alba, a conserved archaeal chromatin protein, with Sir2 and its regulation by acetylation.
Science
296
, 148-151 (2002).
[Abstract]
[Full Text]