The Roles of ING5 in Regeneration and Maintaining Genomic Stability (in vivo model)

Al Shueili, Buthaina

The Roles of ING5 in Regeneration and Maintaining Genomic Stability (in vivo model)

dc.contributor.advisor	Raibowol, Karl T.
dc.contributor.author	Al Shueili, Buthaina
dc.contributor.committeemember	Jirik, Frank R.
dc.contributor.committeemember	Rancourt, Derrick E.
dc.date	2023-11
dc.date.accessioned	2023-08-25T17:50:44Z
dc.date.available	2023-08-25T17:50:44Z
dc.date.issued	2023-08
dc.description.abstract	In this thesis, we provide the first in vivo description of the functions of ING5, a member of the INhibitor of Growth (ING1-5) proteins that are epigenetic regulators. INGs target histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to the H3K4Me3 mark of active transcription. ING5 targets MOZ/MORF and HBO1 HAT complexes to acetylate H3 and H4 core histones, respectively, affecting gene expression. Previous in vitro studies by us and others indicated that ING5 maintains stem cell character in normal and cancer stem cells. Moreover, ING5 has also been implicated in maintaining genomic stability by regulating post-translational modification of DNA repair proteins. Here we find that CRISPR/Cas9 ING5 knockout (KO) mice are sub-fertile but viable and show no decrease in lifespan despite signs of depleted stem cell pools in their brains, skin and peripheral nerves. Cardiac Fibroblasts established from knockout animals had accelerated growth rates, with higher heart fibrosis after an infarct injury. Evidence of chondrogenesis was also obtained in knockout hearts that had compromised heart function, indicating the significance of ING5 for heart integrity. Depletion of ING5 also affected DNA repair, as suggested by the accumulation of DNA damage and apoptosis in the testis, which affected animal fertility. Furthermore, middle-aged to old KO animals develop lymphomas at a rate approximately 6-fold higher than control mice. This may be due to loss of ING5 resulting in p53 instability, with several tissues showing very low or undetectable levels of p53 despite normal levels of p53 mRNA.
dc.identifier.citation	Al Shueili, B. (2023). The roles of ING5 in regeneration and maintaining genomic stability (in vivo model) (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/116904
dc.identifier.uri	https://dx.doi.org/10.11575/PRISM/41746
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Epigenetics
dc.subject	INGs
dc.subject	Stem cells
dc.subject	DNA Damage
dc.subject.classification	Education--Sciences
dc.title	The Roles of ING5 in Regeneration and Maintaining Genomic Stability (in vivo model)
dc.type	doctoral thesis
thesis.degree.discipline	Medicine – Biochemistry and Molecular Biology
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.