Sirtuin-mediated nuclear differentiation and programmed degradation in Tetrahymena

BMC Cell Biology

Emily A Wiley²  Joshua J Smith¹  Kyle A Cottrell¹  Sydney Freggiaro²  Kristin M Slade³ 

[1] Biomedical Sciences Department, Missouri State University, 901 S. National Ave., Springfield, MO 65897, USA;Keck Science Department of Claremont McKenna, Pitzer, and Scripps Colleges, W.M. Keck Science Center, 925 N. Mills Ave., Claremont, CA 91711, USA;Chemistry Department, Hobart and Williams Smith College, 300 Pultney St., Geneva, NY 14456, USA

关键词: histone deacetylase;    ciliate;    Tetrahymena;    HDAC;    sirtuin;    apoptosis;    programmed nuclear degradation;   

Others  :  857070
DOI  :  10.1186/1471-2121-12-40

 received in 2011-04-01, accepted in 2011-09-21,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Slade et al; licensee BioMed Central Ltd.

【 图 表 】

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