Skip to main content
Doctoral thesis, 2014

Bioinformatics studies on the mechanisms of gene regulation in vertebrates

Ghazal, Awaisa

Abstract

Gene regulation implicates an important role in organismal complexity through contributing to phenotypic variation. In my thesis, I studied three diverse components of gene regulatory networks including transcription factors, DNA methylation and microRNAs to elucidate their role in vertebrates. The first three studies concern a recently identified transcription factor called ZBED6 and the fourth study is based on analysis of chicken miRNAs. First study focused on phylogenetic reconstruction of the ZBED gene family, which is comprised of ZBED1, ZBED2, ZBED3, ZBED4, ZBED5 and ZBED6. This study demonstrated that ZBEDs arose from at least two independent transposon domestication events in jawed vertebrate ancestors and also identified a new member of this gene family named C7ORF29. Second study focused on the role of ZBED6 in colon adenocarcinoma. We scanned DNA methylation and RNA sequencing data generated from colon adenocarcinoma tumor and normal tissues. This analysis unraveled a list of potential ZBED6 binding sites that were hypermethylated and showed a negative correlation with gene expression data. This candidate list contained several genes with a known role in cancer development and showed that in addition to the ZBED6 binding sites another transcription factor PAX5 binding sites were located in its close vicinity. In the third study, functional analyses of ZBED6 were performed. This study revealed that ZBED6 regulates muscle proteins by directly regulating IGF2 and Twist2 transcription. Analysis of histone modifications showed that ZBED6 preferentially binds with active promoters to modulate transcriptional activity rather than recruiting repressive histone marks. In the fourth study, potential role of miRNAs in differential growth of two extremely divergent chicken lines was investigated. Our analysis revealed the expression of both known and novel miRNAs in three tissues hypothalamus, liver and pectoralis major muscle of chickens. This study provides a detailed insight into the miRNA expression pattern and suggests an association of miRNAs with growth in chickens. These studies on diverse components will add valuable knowledge to existing information in gene regulatory networks and facilitate in future investigations to reveal regulatory mechanisms underlying diverse biological processes.

Keywords

Bioinformatics; ZBED6; DNA methylation; Colon adenocarcinoma; miRNA; Gene regulation; High and low weight selection lines in chicken; vertebrates; transcription factors

Published in

Acta Universitatis Agriculturae Sueciae
2014, number: 2014:82
ISBN: 978-91-576-8112-6, eISBN: 978-91-576-8113-3
Publisher: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences

Authors' information

Ghazal, Awaisa
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics

UKÄ Subject classification

Bioinformatics and Systems Biology
Evolutionary Biology

URI (permanent link to this page)

https://res.slu.se/id/publ/61764