RNA-dependent regulation of SUV39H1 and constitutive heterochromatin in human cells
Abstract/Contents
- Abstract
- Genome regulation in eukaryotes is largely achieved through the specialization and modification of nucleosomes, the fundamental subunits of chromatin. Gene-poor, repetitive regions of the genome concentrated near centromeres must be transcriptionally silenced by constitutive heterochromatin to maintain genome stability. Constitutive heterochromatin is characterized by H3K9 methylation catalyzed by the SUV39 family of methyltransferase enzymes, and is bound by HP1 proteins to mediate chromatin compaction and transcriptional repression. Although SUV39 proteins have been studied for many years as a model for epigenetic chromatin regulation, the biochemical interactions that govern their association with chromatin and regulate their specificity and stability are not well understood. In this work, we uncover a role for chromatin-associated RNA in localizing SUV39H1 to constitutive heterochromatin in human cells. We find that although transcription is mostly silenced during mitosis, RNA molecules associate with pericentric heterochromatin on mitotic chromosomes, and are transcribed directly from pericentric DNA sequences. The SUV39H1 protein shows the capacity to bind nonspecifically to RNA directly in vitro, associates with pericentric repeat sequencing in cells, and relies on direct binding to RNA for its localization in mitosis as well as interphase. We propose a model in which nonspecific RNA interactions stabilize the interaction between SUV39H1 and chromatin, and together with other interactions such as H3K9me3 binding, regulate and define SUV39H1's sites of action throughout the genome. We strive to further understand the role that SUV39H1-RNA interactions have in heterochromatin function, and to use this system as a model for how noncoding RNAs mediate diverse chromatin-protein connections.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Johnson, Whitney L |
|---|---|
| Associated with | Stanford University, Department of Biochemistry. |
| Primary advisor | Straight, Aaron, 1966- |
| Thesis advisor | Straight, Aaron, 1966- |
| Thesis advisor | Artandi, Steven E |
| Thesis advisor | Das, Rhiju |
| Thesis advisor | Theriot, Julie |
| Advisor | Artandi, Steven E |
| Advisor | Das, Rhiju |
| Advisor | Theriot, Julie |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Whitney L. Johnson. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Whitney Lynn Johnson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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