THESIS
2020
viii, 71 pages : color illustrations ; 30 cm
Abstract
Approximately 40% of the human genome consists of retrotransposons, which are transposable
elements that replicate via an RNA-mediated “copy-and-paste” mechanism. Given their potentially
deleterious effects on the genome, retrotransposons are generally repressed by epigenetic
mechanisms. Intriguingly, a subset of elements has been co-opted to become integral parts of our
genomes, functioning as cis-regulatory elements or as coding sequences. For instance, ERV-derived
SYNCYTIN proteins play a critical role in placental development. Previous studies have
also found retrotransposons to serve as tissue-specific enhancers or alternative promoters in the
human placenta. These studies hint at the potential regulatory functions of retrotransposons in
shaping placental transcriptomes and...[
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Approximately 40% of the human genome consists of retrotransposons, which are transposable
elements that replicate via an RNA-mediated “copy-and-paste” mechanism. Given their potentially
deleterious effects on the genome, retrotransposons are generally repressed by epigenetic
mechanisms. Intriguingly, a subset of elements has been co-opted to become integral parts of our
genomes, functioning as cis-regulatory elements or as coding sequences. For instance, ERV-derived
SYNCYTIN proteins play a critical role in placental development. Previous studies have
also found retrotransposons to serve as tissue-specific enhancers or alternative promoters in the
human placenta. These studies hint at the potential regulatory functions of retrotransposons in
shaping placental transcriptomes and their involvement in placental disorders, including
preeclampsia, a hypertensive pregnancy complication and the leading cause of maternal mortality
due to pregnancy. Despite the abundant examples of retrotransposons’ contribution to the normal
function of the placenta, the role of retrotransposons in placental disorder preeclampsia remains
poorly understood. Here, I generated transcriptomic and epigenomic datasets from 17 control and
preeclampsia-derived placenta samples. I performed an integrative analysis to decipher the cis-regulatory
roles of retrotransposons. Notably, I discovered differentially expressed
retrotransposons in the placenta of preeclampsia patients, which are associated with preeclampsia
pathogenesis. Furthermore, some of the dysregulated retrotransposons can potentially drive novel
transcription. In particular, I identified an MLT1B element that has features of a placenta-specific
promoter for the LIN28B gene, which is dysregulated in the preeclampsia placenta. Taken together,
my thesis work provides insights into the roles of retrotransposons in placenta development and
disorder.
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