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You searched for subject:( Sirtuins genetics). Showing records 1 – 3 of 3 total matches.

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University of California – Berkeley

1. Thurtle, Deborah Mary. The Role of Sirtuins in the Molecular Topography of Silenced Chromatin.

Degree: Molecular & Cell Biology, 2014, University of California – Berkeley

Heterochromatin is key to the appropriate regulation of cell identity. Saccharomyces cerevisiae silent mating loci, HML and HMR, provide a simple, yet elegant model for the regional control of transcriptional repression and its contribution to cell identity. Yeast can be of mating type a or &alpha as is dependent on the alleles at the actively transcribed MAT locus. However, additional copies of the &alpha and a genes are present elsewhere in the genome to facilitate mating-type switching. Interestingly, even though HML and HMR have the exact same promoters as when the genes are at the MAT locus, the genes are not expressed. This promoter-independent repression is due to the Silence Information Regulator (Sir) proteins. Current models of yeast silencing posit that Sir proteins are recruited by transcription factors to HML and HMR. Sir2, whose catalytic activity is necessary for silencing and is the founding member of the sirtuin enzymatic class, deacetylates the neighboring nucleosome creating a high-affinity binding site for the Sir complex. Iterative rounds of this deacetylation results in spreading of Sir proteins across the silenced locus, which is key to silencing. Through a similar mechanism, the Sir-protein complex is also important for silencing telomeres. This nucleation and spreading model for silencing makes testable prediction of silencing. For example, if iterative rounds of deacetylation by Sir2 are necessary for silencing, then a Sir complex would occupy each nucleosome at silenced loci. Additionally, this model only attributes Sir-protein association to HML, HMR and telomeres and not elsewhere in the genome. Lastly, if Sir2's only known role is to deacetylate nucleosome tails then its catalytic activity should be bypassed by preemptively removing these histone acetylations. To test these predictions of the silencing model I have definitively characterized the distribution of Sir proteins throughout the genome and explored the unaccounted role for Sir2's catalytic activity in silencing. By characterizing the distributions of Sir2, Sir3 and Sir4 at high-resolution I have revealed unappreciated nucleation sites for Sir proteins at HML and HMR and a possible higher-order structure critical to silencing. Characterization of Sir proteins across the genome revealed an unanticipated phenomenon of highly-expressed genes being vulnerable to non-specific ChIP enrichment. Lastly, I performed a forward genetic screen to restore silencing independent of Sir2 catalytic activity. This screen identified a non-sirtuin deacetylase as refractory to silencing and suggested the possible role of a non-histone deacetylase substrate as important for silencing. This dissertation work has refined the Saccharomyces cerevisiae silencing model, contributing to our understanding of…

Subjects/Keywords: Genetics; Molecular biology; ChIP-Seq; Heterochromatin; Sir proteins; Sirtuins; Yeast

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Thurtle, D. M. (2014). The Role of Sirtuins in the Molecular Topography of Silenced Chromatin. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/4zm832v6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Thurtle, Deborah Mary. “The Role of Sirtuins in the Molecular Topography of Silenced Chromatin.” 2014. Thesis, University of California – Berkeley. Accessed October 20, 2019. http://www.escholarship.org/uc/item/4zm832v6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Thurtle, Deborah Mary. “The Role of Sirtuins in the Molecular Topography of Silenced Chromatin.” 2014. Web. 20 Oct 2019.

Vancouver:

Thurtle DM. The Role of Sirtuins in the Molecular Topography of Silenced Chromatin. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2019 Oct 20]. Available from: http://www.escholarship.org/uc/item/4zm832v6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Thurtle DM. The Role of Sirtuins in the Molecular Topography of Silenced Chromatin. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/4zm832v6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Huffman, Derek M. Calorie restriction, exercise and body fat : effects on cancer and markers of longevity.

Degree: PhD, 2007, University of Alabama – Birmingham

The benefits of calorie restriction (CR) have historically been attributed to a reduction in food intake. More recently, reduced fat stores have been proposed as an important mediator of CR, spurring interest into the potential for changes in energy expenditure and body composition as a CR mimetic. In order to better understand the relationship of body composition, energetics, cancer and longevity, four separate studies were performed. In Experimental Aim 1, a mouse model of prostate cancer (TRAMP) was used to determine if leanness rather than reduced food intake is responsible for the cancer-preventative effect of CR. It was found that increasing energy expenditure via thermoregulation under fixed-food intake conditions, resulted in smaller, leaner mice, which had less cancer incidence and progression. This finding suggests that in terms of cancer prevention, leanness rather calorie intake per se, is more closely associated with the benefits associated with CR. In Experimental Aim 2, results suggest that the longevity protein SIRT1 is elevated in mouse and human prostate cancer, and may be paradoxically implicated in tumor promotion. Experimental Aim 3 found that liver SIRT1 was not significantly affected by acute or chronic exercise. Finally, the results from Aim 4 found that exercised mice were significantly leaner than their weight-matched counterparts which were calorie restricted. However, CR and exercise had disparate effects on longevity biomarkers, including more favorable changes in the insulin/IGF-1 axis with CR, while exercisers had less DNA damage. The results of this experiment imply that the inability of exercise in prior studies to increase lifespan could be due to a failure to fully mimic the physiologic effects of CR. More studies are needed to determine if the inability of exercise to fully mimic CR is inherent to exercise itself, or if the life-prolonging action of CR work independently of changes in energy balance and body composition.

1 online resource (x, 183 p. : ill., digital, PDF file)

Nutrition Sciences;

Health Professions;

exercise cancer aging longevity caloric restriction obesity

UNRESTRICTED

Advisors/Committee Members: Nagy, Tim R., Bamman, Marcas M.<br>, Elgavish, Ada<br>, Grizzle, William E.<br>, Piyathilake, Chandrika J.<br>, Tollefsbol, Trygve O..

Subjects/Keywords: Adenocarcinoma<; br>; Aging<; br>; Biological Markers  – metabolism<; br>; Caloric Restriction<; br>; Gene Expression Regulation, Neoplastic<; br>; Physical Conditioning, Animal  – physiology<; br>; Prostatic Neoplasms<; br>; Sirtuins  – genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Huffman, D. M. (2007). Calorie restriction, exercise and body fat : effects on cancer and markers of longevity. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,596

Chicago Manual of Style (16th Edition):

Huffman, Derek M. “Calorie restriction, exercise and body fat : effects on cancer and markers of longevity.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 20, 2019. http://contentdm.mhsl.uab.edu/u?/etd,596.

MLA Handbook (7th Edition):

Huffman, Derek M. “Calorie restriction, exercise and body fat : effects on cancer and markers of longevity.” 2007. Web. 20 Oct 2019.

Vancouver:

Huffman DM. Calorie restriction, exercise and body fat : effects on cancer and markers of longevity. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Oct 20]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,596.

Council of Science Editors:

Huffman DM. Calorie restriction, exercise and body fat : effects on cancer and markers of longevity. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,596

3. Workman, Jason J. Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms.

Degree: PhD, Biomedical Sciences, 2016, University of Tennessee Health Science Center

The gene expression profile of a eukaryotic cell is responsive to a variety of extracellular stimuli, including nutrient availability, which allows cells to toggle between anabolism and catabolism based on the favorability of their environment. Much of this information is relayed through signaling complexes, such as the target of rapamycin complex 1 (TORC1), to downstream chromatin modifying enzymes. These enzymes impact the gene regulatory process through altered histone post-translation modifications, changes in chromatin structure, and docking of chromatin regulatory complexes. Yet, despite preliminary studies suggesting that TORC1 affects epigenetic mechanisms, including histone H3 lysine 56 acetylation (H3K56ac), almost nothing is known about how the complex functions in this regard. In this report, we demonstrate that inhibition of TORC1 results in a site-specific reduction in acetylation on N-terminal residues of both histone H3 and H4. This effect is dependent on sirtuin histone deacetylases (HDACs), as inactivation of these enzymes, specifically Hst4, rescues the acetylation defect. We also find that this sirtuin-mediated deacetylation response requires a functional protein phosphatase 6 complex (PP6). PP6 is under direct negative regulation of TORC1, and relief of this inhibition initiates a rapid cytoplasmic to nuclear redistribution of Hst4 which correlates temporally with our observed loss of histone acetylation. The nuclear accumulation of Hst4 precedes an increase in Hst4 protein levels that occurs due to a reduction in Hst4 turnover. Notably, deletion of a subset of sirtuins (hst3Δ or hst4Δ) rescued the sensitivity of a non-essential TORC1 mutant (tco89Δ) to an array of TORC1 inhibitors. This result suggests the link between TORC1 and acetylation may play an essential role in cell cycle regulation and the DNA damage response. We further evaluated whether these TORC1-mediated acetylation marks contribute to the chromatin association of high mobility group proteins (HMGs). And while TORC1-dependent displacement of the HMGs coincides with vacuolar acidification, hyperactivation of TORC1, and significant cell death, it appears to occur independently of TORC1’s regulation of Hst4. We conclude by investigating mitochondrial function in a tco89Δ mutant and mapping the functional domains of Tco89 necessary to sustain TORC1 activity and respond to extracellular stress. Advisors/Committee Members: Ronald N. Laribee.

Subjects/Keywords: Chromatin; Epigenetics; Histone acetylation; Sirtuins; Sit4; Target of Rapamycin; Medical Biochemistry; Medical Cell Biology; Medical Genetics; Medical Sciences; Medicine and Health Sciences

…14 TORC1, sirtuins, and the epigenetic modification of histones… …NUCLEAR ACCUMULATION OF SIRTUINS… …and localization of these factors as was mentioned in the previous sections. TORC1, sirtuins… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Workman, J. J. (2016). Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms. (Doctoral Dissertation). University of Tennessee Health Science Center. Retrieved from https://dc.uthsc.edu/dissertations/408

Chicago Manual of Style (16th Edition):

Workman, Jason J. “Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms.” 2016. Doctoral Dissertation, University of Tennessee Health Science Center. Accessed October 20, 2019. https://dc.uthsc.edu/dissertations/408.

MLA Handbook (7th Edition):

Workman, Jason J. “Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms.” 2016. Web. 20 Oct 2019.

Vancouver:

Workman JJ. Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms. [Internet] [Doctoral dissertation]. University of Tennessee Health Science Center; 2016. [cited 2019 Oct 20]. Available from: https://dc.uthsc.edu/dissertations/408.

Council of Science Editors:

Workman JJ. Environmental Signaling through the Target of Rapamycin Complex 1 (TORC1) and the Regulation of Epigenetic Mechanisms. [Doctoral Dissertation]. University of Tennessee Health Science Center; 2016. Available from: https://dc.uthsc.edu/dissertations/408

.