Τετάρτη, 19 Ιουλίου 2017

Simple sequence repeats showing ‘length preference’ have regulatory functions in humans

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Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Jaya Krishnan, Fathima Athar, Tirupaati Swaroopa Rani, Rakesh Kumar Mishra
Simple sequence repeats (SSRs), simple tandem repeats (STRs) or microsatellites are short tandem repeats of 1–6 nucleotide motifs. They are twice as abundant as the protein coding DNA in the human genome and yet little is known about their functional relevance. Analysis of genomes across various taxa show that despite the instability associated with longer stretches of repeats, few SSRs with specific longer repeat lengths are enriched in the genomes indicating a positive selection. This conserved feature of length dependent enrichment hints at not only sequence but also length dependent functionality for SSRs. In the present study, we selected 23 SSRs of the human genome that show specific repeat length dependent enrichment and analysed their cis-regulatory potential using promoter modulation, boundary and barrier assays. We find that the 23 SSR sequences, which are mostly intergenic and intronic, possess distinct cis-regulatory potential. They modulate minimal promoter activity in transient luciferase assays and are capable of functioning as enhancer-blockers and barrier elements. The results of our functional assays propose cis-gene regulatory roles for these specific length enriched SSRs and opens avenues for further investigations.



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