title: Sirtuin-mediated nuclear differentiation and programmed degradation in Tetrahymena.
abstract: BACKGROUND
  The NAD(+)-dependent histone deacetylases, known as "sirtuins", participate in a variety of processes critical for single- and multi-cellular life. Recent studies have elucidated the importance of sirtuin activity in development, aging, and disease; yet, underlying mechanistic pathways are not well understood. Specific sirtuins influence chromatin structure and gene expression, but differences in their pathways as they relate to distinct chromatin functions are just beginning to emerge. To further define the range of global chromatin changes dependent on sirtuins, unique biological features of the ciliated protozoan Tetrahymena thermophila can be exploited. This system offers clear spatial and temporal separation of multiple whole genome restructuring events critical for the life cycle.
  
  
  RESULTS
  Inhibition with nicotinamide revealed that sirtuin deacetylase activity in Tetrahymena cells promotes chromatin condensation during meiotic prophase, differentiation of heterochromatin from euchromatin during development, and chromatin condensation/degradation during programmed nuclear death. We identified a class I sirtuin, called Thd14, that resides in mitochondria and nucleoli during vegetative growth, and forms a large sub-nuclear aggregate in response to prolonged cell starvation that may be peripherally associated with nucleoli. During sexual conjugation and development Thd14 selectively concentrates in the parental nucleus prior to its apoptotic-like degradation.
  
  
  CONCLUSIONS
  Sirtuin activity is important for several functionally distinct events requiring global chromatin condensation. Our findings suggest a novel role for sirtuins in promoting programmed pycnosis by acting on chromatin destined for degradation. The sirtuin Thd14, which displays physiological-dependent differential localization within the nucleus, is a candidate for a chromatin condensation enzyme that is coupled to nuclear degradation.
authors.affiliation: Keck Science Department of Claremont McKenna, Pitzer, and Scripps Colleges, WM Keck Science Center, Claremont, CA 91711, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Slade
authors.forename: Sydney
authors.initials: S
authors.lastname: Freggiaro
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Cottrell
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Smith
authors.forename: Emily A
authors.initials: EA
authors.lastname: Wiley
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D003227:Conjugation, Genetic / Q000187:drug effects; D053938:DNA Fragmentation; D008540:Meiosis / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000494:pharmacology; D010802:Phylogeny; D055503:Protein Multimerization / Q000187:drug effects; D021381:Protein Transport; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013768:Tetrahymena / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D009536:Niacinamide; D037761:Sirtuins