Epigenetic analysis Of immune associated signaling molecules during mouse retina development

Open Access
Author:
Yang, Chen
Graduate Program:
Anatomy
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
March 19, 2013
Committee Members:
  • Samuel Shaomin Zhang, Thesis Advisor
  • Patricia Mc Laughlin, Thesis Advisor
  • Colin James Barnstable, Thesis Advisor
Keywords:
  • histone modification
  • retina
  • mouse
  • immunity
  • NF-kappaB
  • epigenetics
  • development
Abstract:
The retina is an immune-privileged organ. Many autoimmune diseases, such as age-related macular degeneration, glaucoma, and diabetic retinopathy, are caused by excessive inflammatory responses targeting self-tissue. The physiological functions of extracellular and intracellular signaling molecules of immune responses have been well characterized. The epigenetic aspects of these molecules in the retina, however, have not been well elucidated. In this study, we examined the expression of selected immune-related genes, and their transcriptional accessibility via epigenetic mapping, cluster analysis, and RT-PCR. Among these genes, interleukin receptor related genes and intracellular signaling molecules exhibit higher transcriptional accessibility. Epigenetic mapping of the toll-like receptor (Tlr) family revealed that 3 out of 13 Tlrs exhibit H3K4me2 accumulation during retina development, suggesting that Tlr2, Tlr3, and Tlr9 are the only Tlr members expressed in the retina. Most of the NF-κB signaling molecules exhibited transcriptional accessibility, implying their essential roles in inflammatory regulation during retina maturation. We have also identified two isoforms each of two NF-κB negative feedback regulator genes, Tnfaip3/A20 and Pcbp2, as well as another NF-κB negative feedback regulator gene, Trafd1, that are differentially expressed in mouse retina and spleen in response to lipopolysaccharide treatment.