Variation in gene regulation between animals often explains differences between species and individuals, and perturbed gene expression frequently underlies disease states. Thus, understanding how gene expression is regulated is critical to our understanding of developmental processes, and has been the focus of intense study for many years. Work on enhancer/promoter dynamics has revealed numerous intricacies in transcriptional initiation, including promoter competition, polymerase pausing, and transcriptional bursting. In parallel, computational and experimental analysis of regulatory DNA landscapes has identified an array of cis-regulatory DNA elements, including shadow enhancers, insulators, memory elements, and Polycomb/Trithorax response elements (PRE/TREs). Advances in epigenetics highlight the importance of interaction between chromatin modifying proteins and specific DNA sites such as PRE/TREs in maintaining local gene expression patterns through development, in the absence of early transient transcription factors. Furthermore, in recent years transcriptomic studies have revealed that numerous long non-coding RNAs (lncRNAs) are transcribed from metazoan genomes. lncRNAs have been found to play important and diverse roles in gene regulation. For example, their transcription can alter the activity of underlying cis-regulatory DNA elements. Beyond this lncRNAs can themselves possess diffusible trans functions, binding to chromatin modifying proteins and directing their activity to specific genomic sites. Our current picture of regulated gene expression is still incomplete. Important questions remain, including how long-range enhancer-promoter fidelity is achieved and what underlies tissue-specific chromatin modification. Specifically, how regulatory information is communicated in trans between chromosomes is the focus of this study. Here we propose to use the early Drosophila embryo as a laboratory to dissect the sequences and mechanisms responsible for trans-chromosome regulation at two transvecting Hox gene loci.
We will determine:
Objective 1. How does transcription of Hox lncRNAs regulate Hox gene expression?
Objective 2. How is transcription through Hox regulatory elements communicated between the two chromosomes?
Objective 3. What are the lncRNA associated protein components involved in Hox transcriptional regulation?
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with experience in Developmental Biology and Genetics or with an interest in noncoding RNA and Hox gene function and evolution are encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
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