Characterisation of the first gene promoters to be activated in zebrafish

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Cooper, Ledean (2021). Characterisation of the first gene promoters to be activated in zebrafish. University of Birmingham. Ph.D.

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Abstract

Prior to onset of zygotic genome activation, the genome is held in a state of strict transcriptional repression. Once a threshold nucleo-cytoplasmic (NC) ratio is reached repressive maternally deposited factors are suitably diluted, which in combination with degradation of maternal RNAs by miR-430, provides an environment amenable to global transcription which generally coincides with the mid-blastula transition (MBT) in most animals. Despite this, increasing reports suggest a group of genes are activated before the onset of global zygotic genome activation, with the earliest genes being activated through an as of yet unidentified mechanism.

In order to study the processes that drive expression of a specific subset of genes prior to genome activation, it was necessary to characterise the promoter structure of early expressed genes, of which miR-430 is the most highly and earliest expressed. Identification of characteristic profiles for cis-regulatory elements, such as core and proximal promoter, was done for the purpose of understanding how promoter structure influences the first transcriptional activation in the developing vertebrate embryo.

Here I demonstrate that early genes have a promoter structure distinct from other developmental classes, which suggests they are activated by a distinct mechanism. In regard to miR-430, I have provided evidence for a distinct site with high local concentration of cis-regulatory elements with distinctive epigenetic profile, even compared to other early expressed genes.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):