Acquisition and maintenance of transient imprinted DMRs in the human placenta and their role in development
Genomic imprinting is an epigenetic phenomenon resulting in the monoallelic expression of a subset of genes in a parent-of-origin-specific manner. In general, the promoters of these transcripts contain differentially methylated regions (DMRs), usually methylated on the non-expressed allele. In human...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/663217 |
| Acceso en línea: | http://hdl.handle.net/10803/663217 |
| Access Level: | acceso abierto |
| Palabra clave: | Epigenètica Epigenética Epigenetics Genòmica Genómica Genomics Metilació Metilación Methylation Placenta Creixement humà Crecimiento humano Human growth Ciències de la Salut 575 |
| Sumario: | Genomic imprinting is an epigenetic phenomenon resulting in the monoallelic expression of a subset of genes in a parent-of-origin-specific manner. In general, the promoters of these transcripts contain differentially methylated regions (DMRs), usually methylated on the non-expressed allele. In humans, genome-wide screening experiments indicate that most ubiquitous imprinted genes, associated with DMRs in all tissues, have already been identified. On the contrary, the existence of tissue-specific imprinted DMRs remains mostly uninvestigated. This thesis aims to determine the extent of imprinting in the human placenta and how these genes can influence intrauterine growth and development. During this dissertation, a total of 72 human placenta-specific DMRs were confirmed. All of these regions inherit ethylation from the oocyte and are stable through embryonic reprogramming, being lost after implantation in somatic tissues. Furthermore, we described imprinted monoallelic expression for 20 genes associated with these novel placenta-specific DMRs. Imprinted expression also occurs in the pre-implantation embryo as highlighted by the paternal expression of ZHX3 in cleavage stage embryos. The aberrant expression from the maternal allele of some placenta-specific genes is likely to play an essential role in the hydatidiform mole phenotype since they include crucial genes involved in different biological processes including epigenetic modifications and metabolic processes. In our placenta cohort, we observe polymorphic placenta-specific imprinting, with biallelic expression correlating with biallelic permissive histone marks which can be independent of the allelic methylation state in some cases. Although we have not observed a higher frequency of polymorphic imprinted methylation in placentas from complicated pregnancies or those conceived using assisted reproductive technologies, further characterisation, including extensive quantitative expression studies, are needed to ascertain the role of placenta-specific imprinted genes in development. |
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