| First Author | Aporntewan C | Year | 2013 |
| Journal | Nucleic Acids Res | Volume | 41 |
| Issue | 19 | Pages | 8872-85 |
| PubMed ID | 23935075 | Mgi Jnum | J:210723 |
| Mgi Id | MGI:5571701 | Doi | 10.1093/nar/gkt685 |
| Citation | Aporntewan C, et al. (2013) Upstream mononucleotide A-repeats play a cis-regulatory role in mammals through the DICER1 and Ago proteins. Nucleic Acids Res 41(19):8872-85 |
| abstractText | A-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. |
