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Transposable elements as tissue-specific enhancers in cancers of endodermal lineage
Konsta Karttunen1, Divyesh Patel1,2, Jihan Xia1,2
1Applied Tumor Genomics Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Transposable elements (TEs) can act as enhancers in cancer. This study identifies specific TEs functioning as tissue-specific enhancers in colorectal and liver cancers, revealing their regulatory roles in disease.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Transposable elements (TEs) are repetitive DNA sequences found throughout genomes.
- TEs contain transcription factor (TF) binding sites and are implicated in development and disease.
- Their function as enhancers in cancer is understudied due to genome-wide silencing.
Purpose of the Study:
- To identify transposable elements with functional enhancer activity in human cancers.
- To investigate the tissue-specific roles of TEs as enhancers in colorectal and liver cancers.
- To understand the genomic features and TF binding associated with active TE enhancers.
Main Methods:
- Utilized massively parallel reporter assay (MPRA) data from a whole human genome library.
- Analyzed genomic features, epigenetic marks, and TF binding sites of identified TE enhancers.
- Investigated distinct TE subfamilies (MER11, LTR12) in specific cancer types.
Main Results:
- Identified TEs exhibiting functional enhancer activity in colorectal and liver cancers.
- TE enhancers share characteristics with active enhancers, including epigenetic marks and TF binding.
- Distinct TE subfamilies (MER11 in colon, LTR12 in liver) act as tissue-specific enhancers.
- These TEs are bound by specific TFs and associated with differentially expressed genes.
Conclusions:
- Different cancer types employ distinct transposable elements as tissue-specific enhancers.
- TEs function as bona fide enhancers in cancer genomes, contributing to tissue-specific regulation.
- This work provides a foundation for understanding the broader role of TEs in cancer genomics.
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