Browsing by Author "Wang, Jianrong"

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    Compound cis-regulatory elements with both boundary and enhancer sequences in the human genome
    (Bioinformatics, 2013) Jjingo, Daudi; Wang, Jianrong; Conley, Andrew B.; Lunyak, Victoria V.; Jordan, I. King
    It has been suggested that presumably distinct classes of genomic regulatory elements may actually share common sets of features and mechanisms. However, there has been no genome-wide assessment of the prevalence of this phenomenon. Results: To evaluate this possibility, we performed a bioinformatic screen for the existence of compound regulatory elements in the human genome. We identified numerous such colocated boundary and enhancer elements from human CD4þ T cells.We report evidence that such compound regulatory elements possess unique chromatin features and facilitate cell type-specific functions related to inflammation and immune response in CD4þ T cells.
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    Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression
    (Mobile DNA, 2014) Jjingo, Daudi; Conley, Andrew B.; Wang, Jianrong; Mariño-Ramírez, Leonardo; Lunyak, Victoria V.; Jordan, I. King
    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.