Year: 2014
Type: dissertation
Abstract: Gene regulation implicates an important role in organismal complexity through \ncontributing to phenotypic variation. In my thesis, I studied three diverse components \nof gene regulatory networks including transcription factors, DNA methylation and \nmicroRNAs to elucidate their role in vertebrates. The first three studies concern a \nrecently identified transcription factor called ZBED6 and the fourth study is based on \nanalysis of chicken miRNAs. First study focused on phylogenetic reconstruction of the \nZBED gene family, which is comprised of ZBED1, ZBED2, ZBED3, ZBED4, ZBED5 \nand ZBED6. This study demonstrated that ZBEDs arose from at least two independent \ntransposon domestication events in jawed vertebrate ancestors and also identified a new \nmember of this gene family named C7ORF29. Second study focused on the role of \nZBED6 in colon adenocarcinoma. We scanned DNA methylation and RNA sequencing \ndata generated from colon adenocarcinoma tumor and normal tissues. This analysis \nunraveled a list of potential ZBED6 binding sites that were hypermethylated and \nshowed a negative correlation with gene expression data. This candidate list contained \nseveral genes with a known role in cancer development and showed that in addition to \nthe ZBED6 binding sites another transcription factor PAX5 binding sites were located \nin its close vicinity. In the third study, functional analyses of ZBED6 were performed. \nThis study revealed that ZBED6 regulates muscle proteins by directly regulating IGF2 \nand Twist2 transcription. Analysis of histone modifications showed that ZBED6 \npreferentially binds with active promoters to modulate transcriptional activity rather \nthan recruiting repressive histone marks. In the fourth study, potential role of miRNAs \nin differential growth of two extremely divergent chicken lines was investigated. Our \nanalysis revealed the expression of both known and novel miRNAs in three tissues \nhypothalamus, liver and pectoralis major muscle of chickens. This study provides a \ndetailed insight into the miRNA expression pattern and suggests an association of \nmiRNAs with growth in chickens. These studies on diverse components will add \nvaluable knowledge to existing information in gene regulatory networks and facilitate \nin future investigations to reveal regulatory mechanisms underlying diverse biological \nprocesses.
Author: Awaisa Ghazal
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2152012269