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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2017)

Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, and stress responses. These histone modifications can occur in complex patterns depending on the activity of multiple chromatin modifiers. Histone acetyltransferases (HAT) are one of the classes of chromatin modifiers important for altering chromatin structure and activating transcription. Gcn5 is a highly conserved catalytic subunit found in multiple HAT complexes that regulate gene expression. In addition to HAT activity, phosphorylation of histones and non-histone proteins by protein kinases is also important. Kinases are necessary for signaling pathways such as a rapid response to stress. Here we define previously unsuspected interactions between Gcn5 and different isoforms of the protein kinase CK2, in Saccharomyces cerevisiae. We show that although CK2 has hundreds of targets in vivo, distinctions can be made between the individual catalytic subunits encoded by CKA1 and CKA2. This distinction was found in cells lacking Gcn5. Loss of CKA1 and CKA2 suppresses gcn5∆ mutant sensitivity to elevated temperatures and DNA damage induced by hydroxyurea, respectively. Suppression is lost when either CKB1 or CKB2 are also deleted. Loss of CKA1, but not CKA2 partially recovers the decrease in H3K9,K14ac in gcn5∆ cells. A directed screen of tyrosine residues of core histones demonstrated novel roles of multiple residues, but left unanswered key questions into the interactions seen between Gcn5 and CK2. Together, this work has shown distinct functions of the CK2 isoforms in their roles in specific stress responses and interactions with Gcn5.

    Cover page: The histone acetyltransferase Gcn5 and the multiple personalities of CK2 kinase define new roles in stress response and chromatin function
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2021)
    Purpose: To evaluate the inter- and intra-observer reliability of anterior chamber (AC) angle measurements obtained by swept-source optical coherence tomography (SS-OCT).Methods: Forty-eight consecutive patients diagnosed with primary angle closure suspect (PACS) were included. Three masked observers at different training levels (one glaucoma specialist, one ophthalmology resident, and one pre-medical college student) measured 192 SS-OCT images of the PACS patients. One observer (the glaucoma specialist) repeated measurements 1 week later. SS-OCT parameters included: Anterior segment volume, including corneal, AC, and iris volume; anterior segment dimensions, including AC depth and width (ACD, ACW), and lens vault (LV); and angle parameters, including angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and the trabecular iris angle (TIA). Intraclass correlation coefficients (ICCs) were used to measure reliability.Results: For inter-observer reproducibility, ICCs of corneal, AC, and iris volumes were 0.952 to 0.998. ICCs of ACD at all axes were above 0.989. ICCs of ACW and LV were smallest in the 90°-270° axis (0.751 and 0.768) but not significantly different from other axes. ARA, TISA, and TIA at all angles had significantly smallest ICCs 250 µm from the scleral spur compared with 500 µm and 750 µm. The ICCs comparing observers with different training levels had similar ranges and followed similar trends. For intra-observer repeatability, the smallest ICC was 0.843. Decreasing AC depth correlated with increased inter-observer reproducibility.Conclusions: We found excellent intra-observer repeatability for all SS-OCT parameters. Angle measurements have more variation among the observers when taken 250 µm from the scleral spur. Shallow AC might lead to more variability for angle parameters. Non-expert observers may be recruited for high-quality image grading with standard training.
      Cover page: Repeatability and Reproducibility of Anterior Chamber Angle Measurement with Swept-Source Optical Coherence Tomography in Patients with Primary Angle Closure Suspect
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