Abstract
BackgroundGenome-wide repeat sequences, such as LINEs, SINEs and LTRs share a considerable part of the mammalian nuclear genomes. These repeat elements seem to be important for multiple functions including the regulation of transcription initiation, alternative splicing and DNA methylation. But it is not possible to study all repeats and, hence, it would help to short-list before exploring their potential functional significance via experimental studies and/or detailed in silico analyses.ResultWe developed the ‘Genomic Repeat Element Analyzer for Mammals’ (GREAM) for analysis, screening and selection of potentially important mammalian genomic repeats. This web-server offers many novel utilities. For example, this is the only tool that can reveal a categorized list of specific types of transposons, retro-transposons and other genome-wide repetitive elements that are statistically over-/under-represented in regions around a set of genes, such as those expressed differentially in a disease condition. The output displays the position and frequency of identified elements within the specified regions. In addition, GREAM offers two other types of analyses of genomic repeat sequences: a) enrichment within chromosomal region(s) of interest, and b) comparative distribution across the neighborhood of orthologous genes. GREAM successfully short-listed a repeat element (MER20) known to contain functional motifs. In other case studies, we could use GREAM to short-list repetitive elements in the azoospermia factor a (AZFa) region of the human Y chromosome and those around the genes associated with rat liver injury. GREAM could also identify five over-represented repeats around some of the human and mouse transcription factor coding genes that had conserved expression patterns across the two species.ConclusionGREAM has been developed to provide an impetus to research on the role of repetitive sequences in mammalian genomes by offering easy selection of more interesting repeats in various contexts/regions. GREAM is freely available at http://resource.ibab.ac.in/GREAM/.
Highlights
Repetitive sequences are known to occupy significant portions of the genomes of many complex multicellular organisms [1]
Kunarso et al [14] indicated significant contribution of transposable elements to the occurrence of some of the transcription factor (OCT4 and NANOG) binding sites. They suggested that transposable elements have incorporated new genes into the core regulatory network of embryonic stem cells in humans and mice, and that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells
This suggestion was made because such elements contributed to at least 5.5% of the mammal-exclusive nonexonic conserved elements located in the gene deserts with a strong preference for the neighborhood of genes involved in the development and transcriptional regulation
Summary
Repetitive sequences are known to occupy significant portions of the genomes of many complex multicellular organisms [1]. Kunarso et al [14] indicated significant contribution of transposable elements to the occurrence of some of the transcription factor (OCT4 and NANOG) binding sites. They suggested that transposable elements have incorporated new genes into the core regulatory network of embryonic stem cells in humans and mice, and that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells. Genome-wide repeat sequences, such as LINEs, SINEs and LTRs share a considerable part of the mammalian nuclear genomes These repeat elements seem to be important for multiple functions including the regulation of transcription initiation, alternative splicing and DNA methylation. It is not possible to study all repeats and, it would help to short-list before exploring their potential functional significance via experimental studies and/or detailed in silico analyses
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