Characterization of lysine methylation in epigenetic regulation
Abstract/Contents
- Abstract
- Chromatin is the physiological template for all DNA processing events in eukaryotic cells. Dynamic regulation of chromatin between open and silent states determines the accessibility of underlying DNA to transcription factors or other effector proteins and hence influences biological processes epigenetically without alterations of DNA sequences. The dynamics of chromatin structure regulates diverse cellular functions, and the disruption of chromatin homeostasis is thought to fundamentally impact on the development and progression of cancers and other human diseases. One principal mechanism for regulating chromatin structure involves the reversible covalent post-translational modification of histone proteins by chemical moieties such as acetyl-, methyl- and phospho- groups. In recent years, emerging evidence has suggested a key role of lysine methylation in the regulation of dynamic chromatin structure. Various histone methyl marks orchestrate proper programming of the genome, and aberrant methylation signaling is implicated in the initiation and the progression of various types of cancers. In this article, we described the development of a novel microarray-based high-throughput methodology, human epigenome microarray platform (HEMP), to discover rapidly and accurately methyl lysine-sensitive readers. A number of proteome-wide studies were performed utilizing HEMP as screening approach, and many novel interactions were identified since the establishment of this powerful technology. Utilizing HEMP as screening approach, we identified that the non-canonical Plant Homeodomain (PHD) finger of recombination activating gene 2 (RAG2) specifically recognizes histone H3 tri-methylated at lysine 4 (H3K4me3), revealing for the first time the molecular link between histone methylation and V(D)J recombination. In addition, this article described the characterization of a protein lysine methyltransferase, NSD2, demonstrating the molecular mechanisms by which overexpression of NSD2 contributes to multiple myeloma pathogenesis. This study established biological and pathologic modes of action for NSD2 and presented a novel mechanism by which disruption of chromatin homeostasis contributes to cancer.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kuo, Jen-Hao | |
|---|---|---|
| Associated with | Stanford University, Department of Biology. | |
| Primary advisor | Gozani, Or Pinchas | |
| Thesis advisor | Gozani, Or Pinchas | |
| Thesis advisor | Chua, Katrin Faye | |
| Thesis advisor | Jones, Patricia | |
| Thesis advisor | Utz, Paul | |
| Advisor | Chua, Katrin Faye | |
| Advisor | Jones, Patricia | |
| Advisor | Utz, Paul |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Alex Jen-Hao Kuo. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Jen-Hao Kuo
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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