Roles of the histone methyltransferase complex PRC2 during retinal development in xenopus

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Title Roles of the histone methyltransferase complex PRC2 during retinal development in xenopus
Publication Type dissertation
School or College School of Medicine
Department Neurobiology & Anatomy
Author Al Diri, Issam Abdulghanii
Date 2011-08
Description Much has been done to define and characterize the mechanisms that control the fate of multipotent retinal progenitors during eye development, but our understanding of this process is still nascent. The histone methyltransferase complex PRC2 is a key regulator of differentiation during the development of organs such as skin and cortex, but its roles in vertebrate retinogenesis have not been explored. My work focused on investigating the possible involvement of PRC2 in the progression of retinal progenitors from proliferation to differentiation during eye development in Xenopus laevis embryos. In the first chapter, I report the cloning of Xenopus Suz12, and determine its expression pattern during development. Xsuz12 is provided maternally and its expression persists as development progresses, particularly in the developing central nervous system. Comparative analysis of the PRC2 core subunits Xez, Xeed, Xsuz12 and Xrbbp4 suggests that their expression largely overlaps in the nervous system. In the second chapter, I characterize in detail the retinal expression of the PRC2 core subunits, and explore its potential roles during development using a loss of function approach. I show that the transcripts of the PRC2 core subunits are coincidently expressed in retinal progenitors and are downregulated upon retinal differentiation. Surprisingly, I found that the levels of the H3K27me3 mark that is catalyzed by PRC2 greatly increase in terminally differentiated cells. Loss of PRC2 function led to a marked decrease in H3K27me3 in retinal cell types. Blocking the translation of the core subunits Xez or Xsuz12 caused a reduction in eye size, inhibition of differentiation genes and a bias toward generation of late born cell types. ChIP-seq analysis on whole embryos revealed that H3K27me3 transiently and selectively decorates a subset of genes expressed in the eye, some of which are known negative regulators of retinal differentiation. In the third chapter, I characterize the expression pattern of the newly identified binding partner of PRC2, Xjarid2, in the developing nervous system of Xenopus and found that it is particularly expressed in differentiated cells. Preliminary loss of function analysis suggests that Xjarid2 is required for neural differentiation, in agreement with data on PRC2 core subunits. Taken together, my data indicate that the PRC2 complex is an important regulator of retinal neurogenesis in Xenopus and highlights the contribution of histone methylation to the regulation of retinal proliferation and differentiation.
Type Text
Publisher University of Utah
Subject MESH Xenopus; Embryonic Structures; Morphogenesis; Neurogenesis; Eye Proteins; Retina; Gene Expression Regulation, Developmental; Chromatin Assembly and Disassembly; Photoreceptor Cells; Retinal Ganglion Cells; Basic Helix-Loop-Helix Transcription Factors; Histone Code; Repressor Proteins; Retinogenesis
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Roles of the Histone Methyltransferase Complex in PRC2 During Retinal Development in Xenopus. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Issam Abdulghani Al Diri 2011
Format application/pdf
Format Medium application/pdf
Format Extent 9,553,122 bytes
Source Original in Marriott Library Special Collections,
ARK ark:/87278/s6j70r3b
Setname ir_etd
ID 196278
Reference URL https://collections.lib.utah.edu/ark:/87278/s6j70r3b
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