Investigation of the Role of Insulator Binding Protein CTCF in Lytic HSV-1 Replication

MISSING IMAGE

Material Information

Title:
Investigation of the Role of Insulator Binding Protein CTCF in Lytic HSV-1 Replication
Physical Description:
1 online resource (91 p.)
Language:
english
Creator:
Lilly, Cameron L
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Medical Sciences, Immunology and Microbiology (IDP)
Committee Chair:
BLOOM,DAVID C
Committee Co-Chair:
SWANSON,MAURICE S
Committee Members:
CONDIT,RICHARD C
RENNE,ROLF FRIEDRICH
HUANG,SUMING

Subjects

Subjects / Keywords:
chip -- chromatin -- ctcf -- herpes -- hsv-1 -- insulator -- lytic -- sirna
Immunology and Microbiology (IDP) -- Dissertations, Academic -- UF
Genre:
Medical Sciences thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Lytic replication of Herpes Simplex Virus type 1 can proceed in many different tissues. Latency of this virus, however, can only occur in a very specialized subset of sensory neurons. During both lytic replication and latency, the HSV-1 genome subverts and appropriates cellular processes to associate with chromatin proteins such as histones. To keep differentially regulated regions of chromatin separate during latency, HSV-1 encodes a number of DNA sequences which bind the cellular protein CTCF. One such sequence, known as B2, possesses the ability to perform enhancer blocking function. CTCF is known to coordinate gene expression during development and regulate genes in somatic cells, and also known to be involved in KSHV and EBV latency and in reactivation, and this interaction has been shown to be remodeled during reactivation. During lytic replication of HSV-1, the binding of host chromatin proteins is less organized. Histone proteins are associated with the HSV-1 genome, so it stands to reason that other chromatin factors may assemble on the HSV-1 genome even if the genome is not destined for latency. This, taken with what is known from the gammaherpesviruses studied, suggest CTCF may act in coordinating herpesviral gene expression. In this study we strove to determine if CTCF is a factor in coordinating temporal gene expression during HSV-1 lytic infection. This study showed that CTCF binds not only to CTCF binding sequences during lytic replication, but CTCF binding decreases dramatically as DNA replication occurs. Enrichment of CTCF on the HSV-1 genome correlates with transcription from the genome as a mutant lacking a critical transcriptional activator, KD6, has a static binding pattern of CTCF. Finally, if CTCF is depleted from the cells prior to infection, amounts of HSV-1 DNA increase and viral gene expression is altered as a result. These studies suggest that CTCF association with the genome is mutually exclusive to lytic replication and gives CTCF a potential role for transcriptional control during lytic infection.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Cameron L Lilly.
Thesis:
Thesis (Ph.D.)--University of Florida, 2014.
Local:
Adviser: BLOOM,DAVID C.
Local:
Co-adviser: SWANSON,MAURICE S.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-11-30

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2014
System ID:
UFE0046319:00001