Ageing, either natural or disease-driven, is accompanied by global epigenetic changes including the disruption of silent heterochromatin. Recently, a physical and functional connection has been made between the chromatin changes that occur as cells age and the NuRD chromatin remodeling complex. NuRD is a unique chromatin modifying complex in that it harbors the physical association of histone deacetylase as well as nucleosome remodelling activity. While seemingly absent from budding yeast, a highly similar complex, SHREC, has been purified from the fission yeast S. pombe which appears to regulate heterochromatin in a manner similar to mammalian NuRD. This proposal seeks to investigate the molecular and biochemical basis for SHREC- dependent spreading of heterochromatin using the tractability of yeast genetics and in vitro biochemistry with the intent of characterizing the importance of conserved chromatin binding modules as well as activity of the complex in modifying nucleosomal substrates.

Public Health Relevance

As cells age, they accumulate chromatin defects that lead to DNA damage and alteration of gene expression. Determining the precise mechanisms regulating these epigenetic changes should prove useful in the understanding and possible therapeutic intervention of normal and hyper-accelerated ageing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG038153-02
Application #
8366396
Study Section
Special Emphasis Panel (ZRG1-F08-E (20))
Program Officer
Guo, Max
Project Start
2011-09-20
Project End
2014-09-19
Budget Start
2012-09-20
Budget End
2013-09-19
Support Year
2
Fiscal Year
2012
Total Cost
$32,158
Indirect Cost
Name
University of Tennessee Health Science Center
Department
None
Type
Other Domestic Higher Education
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Creamer, Kevin M; Job, Godwin; Shanker, Sreenath et al. (2014) The Mi-2 homolog Mit1 actively positions nucleosomes within heterochromatin to suppress transcription. Mol Cell Biol 34:2046-61