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Title: Investigation of transcriptional and post-transcriptional regulation of myogenesis
Author: Koutsoulidou, Andrie
ISNI:       0000 0004 2722 619X
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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Skeletal myogenesis IS a complicated and tightly regulated process, at both transcriptional and post-transcriptional levels. Muscle cells isolated from different stages of the human foetal development displayed increased capacity to differentiate in vitro at late stages of the development. Twist is an early developmental transcription factor shown to inhibit muscle differentiation in mice. Endogenous human TWIST (H-TWIST) protein levels were found to be inversely proportional to the state of foetal muscle development and the capacity of isolated myoblasts to differentiate in vitro. Investigation of H-TWIST gene transcriptional regulation revealed that endogenous MyoD binds to the H- TWIST promoter and inhibits its expression. Overexpression of MyoD increased the low capacity of human foetal myoblasts to differentiation in vitro and decreased the levels of H- TWIST protein. These results propose a mechanism by which MyoD downregulates the expression of H-TWIST gene, thus promoting myogenesis. MicroRNAs are non-coding RNA molecules that post-transcriptionally regulate many cellular processes. MiR-l, miR- 133a, miR-133b and miR-206, also known as myomiRs, are expressed in muscle tissue and induced during muscle cell differentiation. MyomiRs were found to be increased during late stages of human foetal muscle development. Increases in their expression levels were proportional to the capacity of myoblasts to differentiate in vitro. Changes in myomiR levels during human foetal development were accompanied by endogenous alterations in their known targets and also in their inducer, MyoD. Overexpression of the latter resulted in an induction of muscle cell differentiation in vitro, accompanied by an increase in the levels of miR-l, miR-133a, miR-133b and miR-206. Myotonic dystrophy type 1 is a muscular dystrophy characterized by impaired muscle cell differentiation. Muscle cells isolated from DMl patients from distinct developmental stages showed a reduction in the expression levels of myomiRs during both differentiated and undifferentiated stages, verifying their important role during myogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available