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Histone Deacetylase Inhibitors Prevent Nucleosome Redistribution at Transcription Start Sites

Title: Histone Deacetylase Inhibitors Prevent Nucleosome Redistribution at Transcription Start Sites.
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Name(s): Pickeral, Crystal, author
Biological Science
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2011
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Identifier: FSU_migr_uhm-0034 (IID)
Keywords: Histone deacetylase inhibitors, Nucleosome distribution, Inflammation
Note: Butyrate and valproic acid are two histone deacetylase inhibitors (HDACi) that act to block acetyl groups from being removed from histone tails. Butyrate is a major energy source for intestinal epithelial cells (IEC) and is produced naturally by commensal bacteria in the gut. Valproic acid is administered clinically for bipolar disorder, however it is under consideration as a promising therapy for inflammatory diseases. It has been shown that HDACi have antiinflammatory properties, yet the link between the anti-inflammatory properties of these class I HDAC inhibitors and their effects on chromatin structure is poorly understood. The study of the impact of class 1 HDAC inhibitor treatment on chromatin structure will illuminate the pathology of inflammatory disorders as well as provide insight into their anti-inflammatory properties. To assess the alterations in chromatin structure induced by HDAC inhibitors, PMA differentiated U937 cells were treated with either 2mM butyrate or 1mM valproic acid in the presence or absence of an immune insult, Lipopolysaccharide (LPS). We monitored nucleosome distribution with an innovative use of whole gene tiling microarrays. Herein we show that HDACi treatment induces modest changes in chromatin structure at the transcription start sites of inflammatory genes. Notably, our results indicate that HDAC inhibitors restrict changes in chromatin structure that an inflammatory insult would induce, suggesting that HDACi "lock-in" chromatin structural states. These studies suggest that the anti-inflammatory mechanisms of HDACi involve regulation of chromatin structure.
Submitted Note: A Thesis submitted to the Department of Biology in partial fulfillment of the requirements for the degree of Honors in the Major.
Degree Awarded: Spring Semester, 2011.
Date of Defense: April 14, 2011.
Subject(s): Biology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_uhm-0034
Restrictions on Access: http://creativecommons.org/licenses/by-nc-nd/3.0/
Host Institution: FSU
Is Part of Series: Honors Theses.

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Pickeral, C. (2011). Histone Deacetylase Inhibitors Prevent Nucleosome Redistribution at Transcription Start Sites. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_uhm-0034