THESIS
2020
xx, 133 pages : color illustrations ; 30 cm
Abstract
Endogenous retroviruses (ERVs) are remnants of ancestral retroviruses that serve as a rich
repertoire of cis-regulatory elements in normal development and disease. While epigenetically
silenced in somatic cells, ERVs could become reactivated as transcriptional enhancers and/or
promoters to drive oncogenesis. Hepatocellular carcinoma (HCC) is the predominant form of
liver cancer and hepatitis B virus (HBV) infection is the leading risk factor in HCC development.
Previous studies have established a link between ERV dysregulation and hepatocarcinogenesis
but a comprehensive survey of the cis-regulatory activities of ERVs and their functional
relevance in HCC and HBV-associated HCC (HBV-HCC) are lacking. Here, I attempted to
decipher the cis-regulatory role of ERVs in HCC and HBV-HC...[
Read more ]
Endogenous retroviruses (ERVs) are remnants of ancestral retroviruses that serve as a rich
repertoire of cis-regulatory elements in normal development and disease. While epigenetically
silenced in somatic cells, ERVs could become reactivated as transcriptional enhancers and/or
promoters to drive oncogenesis. Hepatocellular carcinoma (HCC) is the predominant form of
liver cancer and hepatitis B virus (HBV) infection is the leading risk factor in HCC development.
Previous studies have established a link between ERV dysregulation and hepatocarcinogenesis
but a comprehensive survey of the cis-regulatory activities of ERVs and their functional
relevance in HCC and HBV-associated HCC (HBV-HCC) are lacking. Here, I attempted to
decipher the cis-regulatory role of ERVs in HCC and HBV-HCC using multidimensional
epigenomic datasets. I observed the acquisition of enhancer and/or promoter chromatin features
at a subset of ERVs that in HCC and HBV-HCC. I demonstrated that specific ERV families and
subfamilies gain active enhancer and/or promoter marks, suggesting activation of selected elements during hepatocarcinogenesis. Loss of histone 3 lysine 9 trimethylation (H3K9me3)
and DNA methylation do not accompany the activation of candidate ERVs. The data implicate
that additional regulatory factors are involved in their activation. Moreover, short-interspersed
nuclear elements (SINEs), but not ERVs, preferentially gain active enhancer marks in HBV-HCC.
Collectively, these findings shed light on the cis-regulatory activities of retrotransposons
in hepatocarcinogenesis and the distinct regulation of ERVs in HCC and HBV-HCC.
Post a Comment