Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The Role of Genomic Imprints in Placental Biology

Koppes, Erik (2016) The Role of Genomic Imprints in Placental Biology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (5MB)


Genomic imprinting is a process by which heritable epigenetic marks at a subset of genomic loci are established in a sex-specific manner in parental gametes and then maintained in nascent offspring. This study probes the poorly understood function of genomic imprints in placental biology. Genomic imprints are responsible for the regulation of parent-of-origin specific monoallelic expression of clusters of imprinted genes. The primary epigenetic mark that distinguishes parental alleles at imprinted loci is 5-methylcytosine in the context of cytosine-guanine (CpG) dinucleotides within differentially methylated domains (DMDs). The Dnmt1 gene encodes the maintenance DNA methyltransferase, an enzyme responsible for replicating CpG methylation that is critical throughout the process of genomic imprinting. Genetic disruption of the oocyte specific isoform of Dnmt1 (Dnmt1o) results in partial and wide-spread loss of DMD methylation during preimplantation development and has strong effects on embryonic and extraembryonic development. In this dissertation the morphology of DNMT1o-deficient placentas is examined and their abnormal phenotypes correlated with loss of methylation at specific DMDs. A strong association between loss of methylation at the Kcnq1 DMD and accumulation of trophoblast giant cells was made. In addition, an association between loss of methylation at the Peg10 DMD and loss of fetal viability and placental labyrinthine volume was made. In conjunction with my study of the Dnmt1Δ1o model, I have engineered a novel targeted deletion of the imprinted Klf14 gene and found it has an effect on placental growth. My thesis unambiguously shows that genomic imprints are essential for placental development.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Koppes, Erikeak062@gmail.comEAK37000-0002-4175-7777
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorChaillet, J Richardchaillet@pitt.eduCHAILLET
Committee ChairHildebrand, Jeffrey D.jeffh@pitt.eduJEFFH
Committee MemberChapman, Deborahdlc7@pitt.eduDLC7
Committee MemberApodaca, Gerardgla6@pitt.eduGLA6
Committee MemberBarak, YaakovBaraky@mwri.magee.eduYAB5
Date: 20 May 2016
Date Type: Publication
Defense Date: 19 April 2016
Approval Date: 20 May 2016
Submission Date: 3 May 2016
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 293
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Integrative Molecular Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Genomic Imprints, Genomic Imprinting, Placenta, Mouse, DNMT1, DNA methylation, Peg10, Kcnq1, Mest, Klf14, preimplantation, spongiotrophoblast, labyrinth,
Date Deposited: 20 May 2016 15:15
Last Modified: 19 Dec 2016 14:43


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item