Chatchawit AporntewanPiyapat Pin-OnNachol ChaiyaratanaMonnat PongpanichViroj BoonyaratanakornkitApiwat MutiranguraChulalongkorn UniversityKing Mongkut's University of Technology North BangkokMahidol University2018-10-192018-10-192013-10-01Nucleic Acids Research. Vol.41, No.19 (2013), 8872-888513624962030510482-s2.0-84886075159https://repository.li.mahidol.ac.th/handle/20.500.14594/31200A-repeats are the simplest form of tandem repeats and are found ubiquitously throughout genomes. These mononucleotide repeats have been widely believed to be non-functional 'junk' DNA. However, studies in yeasts suggest that A-repeats play crucial biological functions, and their role in humans remains largely unknown. Here, we showed a non-random pattern of distribution of sense A- and T-repeats within 20 kb around transcription start sites (TSSs) in the human genome. Different distributions of these repeats are observed upstream and downstream of TSSs. Sense A-repeats are enriched upstream, whereas sense T-repeats are enriched downstream of TSSs. This enrichment directly correlates with repeat size. Genes with different functions contain different lengths of repeats. In humans, tissue-specific genes are enriched for short repeats of <10 bp, whereas housekeeping genes are enriched for long repeats of ≥10 bp. We demonstrated that DICER1 and Argonaute proteins are required for the cis-regulatory role of A-repeats. Moreover, in the presence of a synthetic polymer that mimics an A-repeat, protein binding to A-repeats was blocked, resulting in a dramatic change in the expression of genes containing upstream A-repeats. Our findings suggest a length-dependent cis-regulatory function of A-repeats and that Argonaute proteins serve as trans-acting factors, binding to A-repeats. © 2013 The Author(s) 2013.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1093/nar/gkt685