The roles of DPPA2, DPPA4 and SMARCA5 in mouse zygotic genome activation, epigenetic reprogramming and development
type: CreativeWork
description: The epigenetic remodelling that takes place in order to transform a fertilised oocyte into an embryo and then a whole organism, is one of the most intriguing cellular transformations in biology. The whole process starts with the meiotic resumption of an oocyte when the translational activation of the dormant mRNAs takes place, followed by their gradual elimination in the zygote, and ending with the full transcriptional activation of the newly reprogrammed embryonic genome. All these complex processes constitute the maternal to zygotic transition (MZT), which is accompanied by the global epigenetic reprogramming of the embryo. In this dissertation, I focus predominantly on the epigenetic factors that potentially contribute to the initiation of transcription, a process also called zygotic genome activation (ZGA). In mice, this takes place in 1 cell embryos – minor ZGA, followed by a burst of transcription - major ZGA, at the 2 cell stage. Previous screens in the lab, using mouse embryonic stem cell (mESC) identified the small DNA binding proteins DPPA2, DPPA4 and the chromatin remodeler SMARCA5 as potential inducers of major ZGA. Here I focus on validating these three factors and I assess their roles in vivo, using conditional knock-out mouse models and a targeted protein depletion system, together with the characterisation of the transcriptomic and epigenetic changes. In Chapter 1, I give an overview of the biological context for my study together with the latest findings, and depict some of the technologies used to describe the changes that take place during epigenetic reprogramming in the early embryo. Chapter 2 outlines the materials and methods used to address my questions, and Chapters 3, 4 and 5 contain a detailed description of my results and their significance in the wider context. Chapter 3 is focused on the definition of comprehensive ZGA gene lists and of control genes, building a base for chapters 4 and 5. Using six published transcriptomics datasets from…
abstract: The epigenetic remodelling that takes place in order to transform a fertilised oocyte into an embryo and then a whole organism, is one of the most intriguing cellular transformations in biology. The whole process starts with the meiotic resumption of an oocyte when the translational activation of the dormant mRNAs takes place, followed by their gradual elimination in the zygote, and ending with the full transcriptional activation of the newly reprogrammed embryonic genome. All these complex processes constitute the maternal to zygotic transition (MZT), which is accompanied by the global epigenetic reprogramming of the embryo. In this dissertation, I focus predominantly on the epigenetic factors that potentially contribute to the initiation of transcription, a process also called zygotic genome activation (ZGA). In mice, this takes place in 1 cell embryos – minor ZGA, followed by a burst of transcription - major ZGA, at the 2 cell stage. Previous screens in the lab, using mouse embryonic stem cell (mESC) identified the small DNA binding proteins DPPA2, DPPA4 and the chromatin remodeler SMARCA5 as potential inducers of major ZGA. Here I focus on validating these three factors and I assess their roles in vivo, using conditional knock-out mouse models and a targeted protein depletion system, together with the characterisation of the transcriptomic and epigenetic changes. In Chapter 1, I give an overview of the biological context for my study together with the latest findings, and depict some of the technologies used to describe the changes that take place during epigenetic reprogramming in the early embryo. Chapter 2 outlines the materials and methods used to address my questions, and Chapters 3, 4 and 5 contain a detailed description of my results and their significance in the wider context. Chapter 3 is focused on the definition of comprehensive ZGA gene lists and of control genes, building a base for chapters 4 and 5. Using six published transcriptomics datasets from…
author: Kubinyecz, Oana Nicoleta
language: eng
keywords: ZGA, mouse development, zygotic genome activation, smarca5, dppa2, dppa4
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-06-07
date modified: 2026-07-22T22:24:03Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.89634