Histone lysine (K) methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. This study has identified Jhd2, a JmjC domain-containing protein, as an H3K4-specific demethylase in budding yeast. In addition, I show that Jhd2 has intrinsic activity to remove all three states of H3K4 methylation in vivo, and can dynamically associate with chromatin to modulate H3K4 methylation levels on both active and repressed genes and in the subtelomeric regions. I also provide evidence that the interaction between the JmjN and JmjC domains in Jhd2 is important for its protein stability, and Not4 (an E3 ubiquitin ligase) monitors the structural integrity of this inter-domain interaction to maintain the overall protein levels of Jhd2. Moreover, I find that the PHD finger of Jhd2 is important for its chromatin association in vivo by binding to the N-terminal region of H2A, suggesting a novel docking site on chromatin for Jhd2. In summary, this study has revealed important insights into the function and regulation of the H3K4 demethylase Jhd2.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03162011-144756 |
| Date | 21 March 2011 |
| Creators | Huang, Fu |
| Contributors | Zu-Wen Sun, Bruce D. Carter, Katherine L. Friedman, Scott W. Hiebert, Conrad Wagner |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03162011-144756/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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