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Title: Investigation of chromatin mechanisms of tissue-specific and developmentally regulated imprinting of Gsα
Author: Hamid, S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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This thesis describes studies regarding the tissue-specific imprinting of Gsα in mice during development, with a further investigation into the epigenetic mechanisms responsible for the regulation of imprinting. I have carried out an extensive expression analysis of all known major Gnas locus transcripts and shown that pairs of reciprocally imprinted genes are co-expressed which suggests that they may also co-regulated. I show that the expressions of Nesp and GnasXL are significantly correlated across all analysed tissues in newborn and adult mice. I further identify a novel short exon located between Exon1A and Gnas exon 1 that is either included in the Exon1A transcript or spliced out to produce an alternative Exon1A isoform. I show that Gsα expression is significantly correlated with both Exon1A transcripts in adult tissues but only with the alternatively spliced isoform in newborn tissues. I further show that this alternative Exon1A isoform is largely absent in an in vitro adipose cell culture models where Gsα imprinting was also not recapitulated. I hypothesise that Gsα imprinting is directly related to the presence of this alternative Gsα transcript. Using a direct sequencing approach, I have shown that Gsα is strongly imprinted in newborn brown adipose tissue (BAT) and that this imprinting is largely lost in adult BAT, thus demonstrating that Gsα imprinting is developmentally regulated. I hypothesise that Exon1A regulated Gsα imprinting and provide preliminary evidence for this by showing that an alternatively transcribed isoform of Exon1A is highly transcribed specifically in newborn BAT and pituitary tissues, two tissues in which Gsα is imprinted, and that Gsα expression is exclusively correlated with expression of this isoform.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available