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Spatiotemporal control of gene expression in Caenorhabditis elegans


Type

Thesis

Change log

Authors

Serizay, Jacques 

Abstract

Cell-type specific regulation of transcription drives the production of the myriad of different cells generated during development. Profiling genome-wide gene expression landscapes in different tissues has improved our understanding of the physiological and pathological processes taking place during development. Yet, the mechanisms underlying cell-type specific transcription are not well understood. Promoters and enhancers are the key loci that orchestrate spatiotemporal patterns of gene expression. Their activities can range from ubiquitous to highly cell-type specific, and their composition and arrangement define the regulatory grammar directing gene transcription across development. More comprehensive in vivo studies of these regulatory grammars would improve our understanding of how different patterns of gene expression are obtained across tissues. Caenorhabditis elegans is an important model organism for studying develop- mental processes. At the beginning of my PhD, I helped characterize the dynamics of gene expression and chromatin activity across development and aging. Follow- ing this, I aimed to identify and characterize the regulatory elements involved in tissue-specific control of transcription in C. elegans. I jointly profiled chromatin accessibility and gene expression landscapes across the five main tissues of the adult nematode. To achieve this, I developed a method to sort fluorescently labelled nuclei from individual C. elegans tissues. Analyzing the datasets I generated, I first showed that around 80% of the regulatory elements in C. elegans are specifically active in subsets of tissues. I then revealed fundamental differences in the genetic structure and regulatory architecture of genes expressed ubiquitously or in individual tissues, and I defined two distinctive regulatory grammars associated with specific sets of genes. I also uncovered striking and unsuspected differences in nucleosome arrangement and sequence features of ubiquitous and germline-specific promoters compared to somatic promoters. Finally, I optimized a single nucleus method to analyze chromatin accessibility and gene expression during embryogenesis and did a pilot study of early embryo development. My work provides a comprehensive resource of chromatin accessibility and transcription patterns in the different tissues of C. elegans. It sheds light on fundamental differences between the mechanisms of transcription regulation of germline-active genes or somatic tissue-specific genes. The outcome of this work will greatly enable and push forward C. elegans transcription regulation research. The first datasets jointly profiling chromatin accessibility and nuclear transcription across the majority of tissues in a multicellular organism will also be of benefit for the broader community studying gene regulation in eukaryotes.

Description

Date

2020-06-15

Advisors

Ahringer, Julie

Keywords

Genomics, Chromatin, Nucleosome, Gene regulation

Qualification

Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Sponsorship
Medical Research Council (1826632)