Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Mobile DNA
Abstract
Mammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements
(TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been
exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence
in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of
enhancer prevalence within genes and tissue-specific expression, along with MIRs’ previous implication as providing
regulatory sequences, suggested a possible link between MIRs and enhancers.
Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the
relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin
environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated
in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs
than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin
environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with
gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of
biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription
factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as
enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional
activity of non-coding RNAs.
Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which
MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as
to the reason for MIRs’ deep evolutionary conservation.
Description
Keywords
Mammalian-wide interspersed repeat (MIR), Human gene expression
Citation
Jjingo, D., Conley, A. B., Wang, J., Mariño-Ramírez, L., Lunyak, V. V., & Jordan, I. K. (2014). Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression. Mobile DNA, 5(1), 1-12. doi:10.1186/1759-8753-5-14