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Bioinformatics studies on the mechanisms of gene regulation in vertebrates

Ghazal, Awaisa (2014). Bioinformatics studies on the mechanisms of gene regulation in vertebrates. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2014:82
ISBN 978-91-576-8112-6
eISBN 978-91-576-8113-3
[Doctoral thesis]

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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.

Authors/Creators:Ghazal, Awaisa
Title:Bioinformatics studies on the mechanisms of gene regulation in vertebrates
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :10 October 2014
Volume:2014:82
Number of Pages:60
Papers/manuscripts:
NumberReferences
I.Hayward, A*., Ghazal, A*., Andersson, G., Andersson, L., and Jern, P. (2013). ZBED evolution: repeated utilization as regulators of diverse host functions. PLoS ONE 8(3): e59940. (*AH and AG contributed equally)
II.Ghazal, A., Wallerman, O., Johansson, A., Andersson, L., Andersson, G., and Molin, A-M. Genome-wide analysis of the DNA methylation landscape in colon adenocarcinoma reveals hyper-methylation at ZBED6-target regions. Manuscript.
III.Jiang, L., Wallerman, O., Younis, S., Rubin, C.J., Gilbert, E.R., Sundstrom, E., Ghazal, A., Zhang, X., Wang, L., Mikkelsen, T.S., Andersson, G. & Andersson, L. (2014). ZBED6 modulates the transcription of myogenic genes in mouse myoblast cells. PLoS One, 9(4), p. e94187.
IV.Ghazal, A., Molin, A-M., Lopes Pinto, FA., De Koning, D-J., Andersson, L., and Andersson, G. Differentially expressed microRNAs in relation to growth of two extremely divergent chicken lines: LWS and HWS. Manuscript.
UNSPECIFIED(*AH and AG contributed equally)
Place of Publication:Uppsala
Publisher:Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8112-6
ISBN for electronic version:978-91-576-8113-3
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
X Agricola extesions > X30 Life sciences
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Bioinformatics and Systems Biology (methods development to be 10203)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Evolutionary Biology
Agrovoc terms:bioinformatics, vertebrates, genes, gene expression, transcription factors, rna, dna, methylation, neoplasms, chickens, selection criteria, body weight
Keywords:Bioinformatics, ZBED6, DNA methylation, Colon adenocarcinoma, miRNA, Gene regulation, High and low weight selection lines in chicken, vertebrates, transcription factors
URN:NBN:urn:nbn:se:slu:epsilon-e-2163
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2163
ID Code:11572
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
External funders:Higher Education Commission, Pakistan
Deposited By: Awaisa Ghazal
Deposited On:16 Oct 2014 06:08
Metadata Last Modified:02 Dec 2014 11:09

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