Understanding intragenic transcription and its regulation

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Lamberte, Lisa Ellevera (2016). Understanding intragenic transcription and its regulation. University of Birmingham. Ph.D.

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Abstract

Transcription is the first step in gene expression. Thus, RNA polymerase copies information from template DNA to generate the mRNA template for protein production. Transcription is divided into three steps; each step provides a platform for regulation of gene expression. This work contributes to understanding novel aspects of regulatory processes.
For example, complex regulation of expression of the nucleoid-associated protein cbpA was found to be dependent not only on sigma factor specificity, but also on binding of the transcription factor Fis upstream of the cbpA start codon. Binding of Fis to the cbpA regulatory region prevents the action of a strong σ70-dependent promoter found within the coding region of a neighbouring gene, yccE. This work carefully dissects the sequence specificity and orientation specificity of DNA sequences found upstream of the cbpA coding region that allows for the binding of Fis. Binding of Fis to the cbpA regulatory region is a redundant process, whereby in the absence of Fis another factor binds to this region. Furthermore, the regulation of cbpA was also found to be dependent on the interplay between the strong σ70-dependent promoter and a weak but convergent σ32-dependent promoter.
Finally, horizontally acquired DNA, which is AT-rich in nature, has been known to be regulated by the transcription factor, H-NS. However, the field only has limited knowledge on the mechanisms behind this regulation. It was previously thought that AT-rich genes are subject to canonical regulation by H-NS. However, this work demonstrates the phenomenon of “pseudo-regulation”. Here, H-NS silences activity coming from intragenic promoters, rather than the genuine promoter. This phenomenon is likely widespread, and is demonstrated by this study in a number of AT-rich genes.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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